What is the recommended dose of antihistamines, such as cetirizine (second-generation antihistamine) or loratadine (second-generation antihistamine), for the treatment of chronic urticaria?

Antihistamine Dosing for Chronic Urticaria

Start with standard-dose second-generation antihistamines (cetirizine 10mg or loratadine 10mg once daily), and if inadequate control occurs after 2-4 weeks, increase the dose up to 4-fold the standard dose before considering other therapies. 1

Initial Treatment Approach

• Begin with once-daily standard dosing of a second-generation H1 antihistamine such as cetirizine 10mg or loratadine 10mg 1
• Offer patients a choice of at least two different nonsedating antihistamines, as individual responses and tolerance vary significantly 1
• Cetirizine reaches maximum concentration fastest, which may be advantageous when rapid symptom control is needed 1

Dose Escalation Strategy

If symptoms remain uncontrolled after 2-4 weeks (or earlier if symptoms are intolerable), increase the antihistamine dose up to 4-fold the standard dose. 1 This approach is supported by:

• Higher doses demonstrate enhanced "antiallergic" effects on mast-cell mediator release, particularly with cetirizine and loratadine 1
• Up-dosing to 4-fold is common practice where potential benefits outweigh risks 1
• In patients who fail 4-fold dosing, 49% achieved adequate control with doses higher than 4-fold (median 8-fold, range 5-12 fold) 2

Specific Updosing Recommendations by Agent:

• Bilastine and levocetirizine: Can be safely up-dosed to 4 times standard dose (Grade A recommendation) 3
• Fexofenadine: Studied and effective at 3 times standard dose (Grade A recommendation) 3
• Cetirizine: Effective up to 4-fold but may cause dose-related sedation at higher doses 1, 3
• Desloratadine and ebastine: Can be up-dosed (Grade B recommendation) 3
• Loratadine: Effective at higher doses with antiallergic properties 1

Treatment Monitoring and Adjustment

• Assess disease control using the Urticaria Control Test (UCT); patients with UCT score ≤16 require dose escalation 1
• Allow 2-4 weeks at each dose level before escalating further 1
• Adjust timing of medication to ensure highest drug levels coincide with anticipated urticaria symptoms 1

Step-Down Protocol

Once complete disease control is achieved (3 consecutive months), consider gradual dose reduction: 1

• Do not step down before completing at least 3 consecutive months of complete control 1
• Reduce by no more than 1 tablet per month 1
• If breakthrough symptoms occur, return to the last dose that provided complete control 1

Important Caveats and Pitfalls

Sedation Risk:

• Cetirizine may cause sedation, especially at higher doses 1, 3
• Fexofenadine, loratadine, and desloratadine do not cause sedation at recommended doses 1
• Avoid combining first-generation antihistamines at bedtime with second-generation agents during the day, as first-generation agents cause prolonged daytime drowsiness despite being dosed at night 4

Renal Impairment:

• Halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate renal impairment 1
• Avoid cetirizine and levocetirizine in severe renal impairment (creatinine clearance <10 mL/min) 1
• Use loratadine and desloratadine with caution in severe renal impairment 1

Pregnancy:

• Loratadine and cetirizine are FDA Pregnancy Category B drugs 1
• Avoid all antihistamines in first trimester when possible 1

Alternative Strategies if Inadequate Response

• Consider switching antihistamines (fexofenadine, loratadine, or desloratadine) rather than increasing frequency, as all second-generation agents have similar efficacy profiles 4
• Adding montelukast 10mg to levocetirizine 5mg once daily equals the efficacy of levocetirizine 10mg alone but with significantly less sedation 4
• H2 antihistamine addition may provide better urticaria control than H1 antihistamine alone 1

Safety Profile of Higher Doses

• Side effects were reported in only 20% of patients receiving up-dosed antihistamines, with somnolence being most common (17%) 2
• Higher than 4-fold dosing showed side effects in only 10% of patients 2
• No dose-dependent increase in adverse effects or systemic complications (including cardiotoxicity) at higher than licensed doses 3

Next Steps if Antihistamines Fail

If inadequate control persists despite 4-fold (or higher) antihistamine dosing, add omalizumab 300mg every 4 weeks as second-line therapy, with potential updosing to 600mg every 2 weeks if needed 1