What are the consequences of taking an overdose of antihistamines, such as Benadryl (diphenhydramine) or Claritin (loratadine)?

Consequences of Taking Too Many Antihistamines

Taking an overdose of antihistamines can lead to serious and potentially life-threatening complications including sedation, cognitive impairment, anticholinergic toxicity, cardiovascular effects, and in severe cases, death.

First-Generation vs. Second-Generation Antihistamines

First-Generation Antihistamines (e.g., Diphenhydramine/Benadryl)

Overdose of first-generation antihistamines poses greater risks due to their ability to cross the blood-brain barrier and their anticholinergic properties:

• Central Nervous System Effects:

  • Severe sedation and drowsiness (occurs in >50% of patients even at therapeutic doses) 1
  • Cognitive impairment and performance deficits
  • Confusion and delirium
  • Paradoxical excitation, especially in children 2
  • Hallucinations
  • Seizures in severe cases

• Anticholinergic Effects:

  • Dry mouth and eyes
  • Blurred vision
  • Urinary retention
  • Constipation
  • Hyperthermia
  • Tachycardia

• Cardiovascular Effects:

  • Tachycardia
  • Hypertension followed by hypotension
  • Potential for arrhythmias in severe overdose

Second-Generation Antihistamines (e.g., Loratadine/Claritin)

While generally safer, overdose of second-generation antihistamines can still cause problems:

• Cardiovascular Effects:

  • Some second-generation antihistamines (particularly terfenadine and astemizole, which are now restricted) can cause QT interval prolongation and potentially fatal cardiac arrhythmias called Torsades de Pointes 2, 3
  • Risk increases with co-administration of drugs that inhibit cytochrome P450 enzymes 2

• Other Effects:

  • Mild sedation (much less common than with first-generation antihistamines)
  • Headache
  • Gastrointestinal disturbances

Risk Factors for Severe Reactions

• Age: Elderly patients and young children are at higher risk for adverse effects 4
• Pre-existing conditions: Patients with glaucoma, prostatic hypertrophy, cardiovascular disease, or impaired liver/kidney function 5
• Drug interactions: Combining antihistamines with alcohol, sedatives, or tranquilizers significantly increases risk 5
• Genetic factors: Some individuals have genetic polymorphisms that make them more susceptible to adverse effects 2

Specific Risks by Antihistamine Type

Diphenhydramine (Benadryl) Overdose

• Most dangerous of commonly available OTC antihistamines
• Significant risk of injury (2.27 times higher than with loratadine) 6
• Sedation reported in approximately 50% of users even at therapeutic doses 7
• FDA warning label specifically mentions risk of accidental overdose requiring immediate medical attention 5

Loratadine (Claritin) and Other Newer Antihistamines

• Generally safer in overdose than first-generation antihistamines 1
• Lower risk of sedation (8% for loratadine vs. 50% for diphenhydramine) 4
• Minimal CNS effects at therapeutic doses
• Less likely to cause serious adverse events in overdose 1

Management of Antihistamine Overdose

• First-generation antihistamine overdose:

  • Requires immediate medical attention
  • Supportive care is the mainstay of treatment
  • No specific antidote exists 1
  • Monitoring for cardiac, respiratory, and CNS complications

• Second-generation antihistamine overdose:

  • Small overdoses (3-4 times normal dose) may be managed at home with monitoring
  • Larger overdoses require medical evaluation
  • Specific monitoring for cardiac effects with certain agents 1

Prevention

• Keep all antihistamines out of reach of children
• Use second-generation antihistamines when possible, especially in elderly patients 4
• Avoid combining antihistamines with alcohol, sedatives, or tranquilizers 5
• Be aware of potential drug interactions, especially with medications that affect liver metabolism 2

Long-term Consequences

• Regular use of first-generation antihistamines has been associated with:
  • Impaired learning and school performance in children 2
  • Increased risk of occupational accidents 2
  • Increased risk of motor vehicle accidents (1.5 times higher risk) 2
  • Potential cognitive effects in elderly patients 4

In summary, while antihistamines are generally safe when used as directed, overdose can lead to significant morbidity and potential mortality, particularly with first-generation agents. Second-generation antihistamines have a better safety profile but are not without risks in overdose situations.