Anti-histamines Used in Pediatrics
Antihistamines in Pediatric Medicine
Antihistamines are a class of drugs widely used in pediatric practice for the management of allergic conditions. They work by blocking the effects of histamine, a key mediator in allergic reactions.
Key Points:
- Primarily used to treat allergic conditions such as allergic rhinitis, urticaria, and atopic dermatitis
- Classified into first-generation (sedating) and second-generation (less-sedating) antihistamines
- Second-generation antihistamines are generally preferred in pediatrics due to their improved safety profile
- Available in various formulations including oral liquids, tablets, and topical preparations
- Efficacy and safety profiles vary among different antihistamines and age groups
Mechanism of Action
Antihistamines exert their effects primarily by antagonizing histamine receptors, particularly the H1 receptor. The mechanism of action includes:
- Competitive antagonism of H1 receptors:
- Bind to H1 receptors, preventing histamine from attaching
- Reduce histamine-mediated allergic symptoms such as itching, sneezing, and rhinorrhea
- Stabilization of mast cells:
- Some antihistamines may reduce histamine release from mast cells
- This effect is more pronounced with long-term use
- Anti-inflammatory effects:
- Inhibition of inflammatory mediator release
- Reduction of eosinophil migration
- Central nervous system effects:
- First-generation antihistamines cross the blood-brain barrier more readily, leading to sedation
- Second-generation antihistamines have limited CNS penetration, reducing sedative effects
Note: The duration of action varies among different antihistamines, influencing dosing frequency and potential for side effects.
Classification and Types
First-Generation Antihistamines:
Also known as sedating antihistamines, these drugs readily cross the blood-brain barrier.
- Diphenhydramine (Benadryl):
- Commonly used for acute allergic reactions and as a short-term sleep aid
- Available in oral and parenteral forms
- Chlorpheniramine:
- Used for allergic rhinitis and urticaria
- Longer duration of action compared to diphenhydramine
- Hydroxyzine:
- Used for pruritus and as an anxiolytic
- Has a significant anticholinergic effect
Second-Generation Antihistamines:
Also known as non-sedating or less-sedating antihistamines, these have limited CNS penetration.
- Cetirizine:
- Commonly used for allergic rhinitis and chronic urticaria
- Available as oral tablets and liquid
- Loratadine:
- Long-acting, used for allergic rhinitis and chronic urticaria
- Available as tablets, rapidly-disintegrating tablets, and liquid
- Fexofenadine:
- Non-sedating, used for allergic rhinitis and chronic urticaria
- Less likely to cause drowsiness than cetirizine
- Desloratadine:
- Active metabolite of loratadine
- Long-acting with minimal sedative effects
Topical Antihistamines:
- Ketotifen eye drops: Used for allergic conjunctivitis
- Azelastine nasal spray: For allergic rhinitis
Indications
Antihistamines are used to treat various allergic conditions in pediatrics:
Primary Indications:
- Allergic rhinitis:
- Both seasonal and perennial forms
- Second-generation antihistamines are first-line treatment
- Urticaria:
- Acute and chronic forms
- Often used in combination with H2 antagonists for severe cases
- Atopic dermatitis:
- For relief of pruritus
- Both oral and topical formulations may be used
- Allergic conjunctivitis:
- Topical antihistamine eye drops are effective
Other Indications:
- Anaphylaxis:
- As an adjunct to epinephrine in the acute management
- Not a substitute for epinephrine in anaphylaxis
- Motion sickness:
- First-generation antihistamines (e.g., dimenhydrinate) are effective
- Insomnia:
- Short-term use of first-generation antihistamines
- Not recommended as a primary treatment for pediatric insomnia
- Cough and cold symptoms:
- Limited efficacy and not recommended in children under 6 years
Age-specific considerations:
- Infants (<2 years): Limited indications, use with caution
- Young children (2-6 years): Second-generation antihistamines preferred
- Older children and adolescents: Wider range of indications and formulations available
Dosing and Administration
Dosing of antihistamines in pediatrics varies based on the specific drug, age, weight, and indication. Always consult current guidelines and package inserts for the most up-to-date dosing information.
Common Second-Generation Antihistamines:
- Cetirizine:
- 6 months - 5 years: 2.5 mg once daily
- 6-11 years: 5-10 mg once daily
- 12 years and older: 10 mg once daily
- Loratadine:
- 2-5 years: 5 mg once daily
- 6 years and older: 10 mg once daily
- Fexofenadine:
- 6 months - 2 years: 15 mg twice daily
- 2-11 years: 30 mg twice daily
- 12 years and older: 60 mg twice daily or 180 mg once daily
Common First-Generation Antihistamines:
- Diphenhydramine:
- 2-5 years: 6.25 mg every 4-6 hours (max 37.5 mg/day)
- 6-11 years: 12.5-25 mg every 4-6 hours (max 150 mg/day)
- 12 years and older: 25-50 mg every 4-6 hours (max 300 mg/day)
- Chlorpheniramine:
- 2-5 years: 1 mg every 4-6 hours (max 6 mg/day)
- 6-11 years: 2 mg every 4-6 hours (max 12 mg/day)
- 12 years and older: 4 mg every 4-6 hours (max 24 mg/day)
Administration Tips:
- Use weight-based dosing when available, especially in younger children
- Consider liquid formulations for younger children who cannot swallow tablets
- Administer second-generation antihistamines at the same time each day for consistent effect
- For seasonal allergies, start treatment before the allergy season begins
Efficacy
The efficacy of antihistamines in pediatric patients has been well-established for various allergic conditions:
Allergic Rhinitis:
- Second-generation antihistamines are highly effective in reducing nasal and ocular symptoms
- Improvement in quality of life scores and reduction in school absenteeism
- Onset of action within 1-2 hours, with effects lasting 24 hours for once-daily formulations
Urticaria:
- Effective in reducing itching and hive formation in acute and chronic urticaria
- Higher doses may be required for complete symptom control in some patients
- Combination with H2 antagonists may provide additional benefit in refractory cases
Atopic Dermatitis:
- Moderate efficacy in reducing pruritus associated with atopic dermatitis
- May help improve sleep in patients with nocturnal itching
- Less effective than topical corticosteroids for overall disease control
Allergic Conjunctivitis:
- Topical antihistamine eye drops provide rapid and effective symptom relief
- Oral antihistamines may also improve ocular symptoms in allergic rhinoconjunctivitis
Comparative Efficacy:
- Second-generation antihistamines are generally as effective as first-generation agents with fewer side effects
- Among second-generation antihistamines, efficacy is generally similar, with individual patient response variability
- Intranasal corticosteroids are more effective than oral antihistamines for nasal symptoms of allergic rhinitis
Factors Affecting Efficacy:
- Adherence to prescribed regimen
- Correct dosing and timing of administration
- Individual patient factors (e.g., severity of allergic condition, comorbidities)
- Environmental control measures (e.g., allergen avoidance)
Safety Profile
Second-Generation Antihistamines:
Generally well-tolerated with a favorable safety profile.
Common Side Effects:
- Mild sedation (less common than with first-generation agents)
- Headache
- Dry mouth
- Gastrointestinal disturbances (nausea, abdominal pain)
Rare Side Effects:
- Prolonged QT interval (particularly with high doses of terfenadine and astemizole, which are no longer available in many countries)
- Behavioral changes (irritability, hyperactivity)
- Allergic reactions
First-Generation Antihistamines:
Have a less favorable safety profile due to their ability to cross the blood-brain barrier.
Common Side Effects:
- Sedation and drowsiness
- Impaired cognitive function and psychomotor performance
- Dry mouth, blurred vision, and urinary retention (anticholinergic effects)
- Dizziness
Rare Side Effects:
- Paradoxical excitation in young children
- Seizures (at high doses)
- Cardiac arrhythmias
Safety Considerations in Pediatrics:
- Use caution in children under 2 years of age
- Avoid use of first-generation antihistamines in children with asthma or other respiratory conditions
- Monitor for behavioral changes, especially when initiating treatment
- Adjust dosing based on weight and age
- Be aware of potential drug interactions, especially with other CNS depressants
Long-term Safety:
- Second-generation antihistamines have a good long-term safety profile
- Regular monitoring is recommended for children on long-term antihistamine therapy
- No significant evidence of tolerance or dependence with long-term use
Clinical Considerations
Choice of Antihistamine:
- Prefer second-generation antihistamines for most indications due to better safety profile
- Consider individual patient factors (age, symptoms, comorbidities) when selecting an antihistamine
- For acute, severe allergic reactions, first-generation antihistamines may be preferred due to faster onset of action
Dosing Considerations:
- Start with the lowest effective dose and titrate as needed
- Consider once-daily dosing options to improve adherence
- Adjust dosing based on response and tolerability
Monitoring:
- Assess efficacy and side effects at follow-up visits
- Monitor growth and development in children on long-term therapy
- Be alert for changes in behavior or academic performance
Special Populations:
- Use with caution in children with hepatic or renal impairment
- Consider potential drug interactions in children with multiple medications
- Exercise caution in children with a history of seizures or cardiac arrhythmias
Patient Education:
- Instruct parents/caregivers on proper administration and potential side effects
- Emphasize the importance of consistent dosing for optimal effect
- Advise on environmental control measures to complement pharmacological treatment
Combination Therapy:
- Consider combining antihistamines with other medications (e.g., nasal corticosteroids) for enhanced efficacy in allergic rhinitis
- Use caution when combining multiple antihistamines or with other sedating medications
When to Refer:
- Refer to an allergist/immunologist for complex cases or poor response to initial therapy
- Consider referral for children with chronic urticaria or severe atopic dermatitis
- Seek specialist consultation for children with multiple drug allergies or anaphylaxis
