What is the recommended dosing and treatment regimen for patients requiring H1 (Histamine 1) and H2 (Histamine 2) blockers?

H1 and H2 Blocker Dosing and Treatment Regimens

For acute allergic reactions and anaphylaxis, combine diphenhydramine 25-50 mg (1-2 mg/kg) parenterally with ranitidine 50 mg IV (1 mg/kg in children, diluted in 5% dextrose over 5 minutes) as second-line therapy after epinephrine, as this combination is superior to H1 blockade alone. 1

Acute Allergic Reactions and Anaphylaxis

H1 Blocker Dosing

• Adults: Diphenhydramine 25-50 mg parenterally 1
• Children: Diphenhydramine 1-2 mg/kg parenterally 1
• Timing: Administer every 4-6 hours as needed, maximum 6 doses in 24 hours 2

H2 Blocker Dosing

• Adults: Ranitidine 50 mg IV over 5 minutes 1
• Children: Ranitidine 12.5-50 mg (1 mg/kg) IV, diluted in 5% dextrose to 20 mL total volume, administered over 5 minutes 1
• Alternative: Cimetidine 4 mg/kg IV for adults (no established pediatric dosing for anaphylaxis) 1

Critical Treatment Principles

• Never use H1 or H2 antihistamines as monotherapy for anaphylaxis—they are second-line agents to epinephrine 1
• Combined H1 and H2 blockade demonstrates significantly better resolution of urticaria and angioedema compared to H1 blockade alone, with 84% versus 75% wheal suppression 3, 4
• The combination reduces heart rate more effectively (10 beats/min reduction versus 6 beats/min with H1 alone at 1 hour) 3

Chronic Urticaria and Mastocytosis

Step-Up Treatment Algorithm

Step 1: Standard-Dose Second-Generation H1 Antihistamine

• Start with cetirizine 10 mg once daily, loratadine 10 mg once daily, or desloratadine 5 mg once daily 1
• Assess control after 2-4 weeks using Urticaria Control Test (UCT score; complete control = UCT >16) 1

Step 2: Increase H1 Antihistamine Dose

• If inadequate control, increase second-generation H1 antihistamine up to 4-fold the standard dose 1
• This approach is now common practice when benefits outweigh risks 1
• Continue for at least 3 consecutive months once complete control is achieved before considering step-down 1

Step 3: Add H2 Blocker

• Famotidine 20 mg twice daily is the preferred H2 blocker 1
• Alternative: Ranitidine or cimetidine at standard doses 1
• The addition of H2 blockers to H1 antihistamines provides better urticaria control than H1 antihistamines alone 1
• H2 blockers are particularly effective for gastrointestinal symptoms accompanying urticaria 1

Step 4: Additional Adjunctive Therapy

• Add cromolyn sodium 200 mg four times daily for gastrointestinal symptoms (diarrhea, abdominal pain, nausea, vomiting) 1
• Consider leukotriene receptor antagonists for refractory skin and gastrointestinal symptoms 1
• Omalizumab 300 mg every 4 weeks (or 600 mg every 2 weeks) if symptoms remain inadequate after 2-4 weeks 1

Specific H1 and H2 Combinations for Mastocytosis

• H1 and H2 blockers control pruritus, flushing, urticaria, angioedema, gastrointestinal symptoms (diarrhea, cramping, nausea), neurologic symptoms (headache, brain fog), cardiovascular symptoms (presyncope, tachycardia), and pulmonary symptoms (wheezing) 1
• Standard doses should be titrated upward for refractory symptoms 1

Step-Down Protocol

When to Consider Step-Down

• Only after achieving at least 3 consecutive months of complete control (UCT >16) 1
• Reduce daily dose by no more than 1 tablet per month 1
• If control is lost during step-down, return to the last dose that provided complete control 1

Special Populations and Considerations

Timing Optimization

• Adjust medication timing to ensure highest drug levels when urticaria is anticipated 1
• Cetirizine has the shortest time to maximum concentration, advantageous when rapid availability is needed 1
• Desloratadine has the longest elimination half-life (27 hours); discontinue 6 days before skin prick testing 1

Sedating Antihistamines

• Adding a sedating H1 antihistamine at night (chlorphenamine 4-12 mg or hydroxyzine 10-50 mg) to a non-sedating H1 antihistamine during the day may improve sleep 1
• This provides little additional clinical effect on urticaria if H1 receptors are already saturated 1
• Avoid first-generation H1 antihistamines in elderly patients due to cognitive decline and sedation risk 5

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

Hepatic Impairment

• Avoid alimemazine (hepatotoxic) and chlorphenamine/hydroxyzine (inappropriate sedation) in severe liver disease 1

Pregnancy

• Avoid all antihistamines when possible, especially in the first trimester 1
• Chlorphenamine is often chosen in the UK due to its long safety record 1
• Loratadine and cetirizine are FDA Pregnancy Category B 1

Common Pitfalls

• Do not use H1 or H2 blockers as monotherapy for anaphylaxis—epinephrine is the first-line treatment 1
• H1 and H2 blockers have much slower onset of action than epinephrine and should never replace it 1
• Do not step down antihistamine doses prematurely (before 3 months of complete control) 1
• H2 blockers alone provide minimal benefit; they must be combined with H1 blockers 1, 4
• The H2 blocker potentiates H1 blocker effects at 2,3,6, and 24 hours, but not at 1 hour 6