What is the alternative antihistamine used intramuscularly (IM) or intravenously (IV) instead of oral diphenhydramine for premedication before rituximab infusion?

Alternative Antihistamines for IV/IM Use Instead of Oral Diphenhydramine for Rituximab Premedication

IV diphenhydramine is the primary alternative antihistamine that should be used when oral administration is not possible for rituximab premedication. 1

First-Line Alternative Option

• IV diphenhydramine: 25-50 mg administered intravenously 30 minutes before rituximab infusion 1
• IM diphenhydramine: 25-50 mg administered intramuscularly when IV access is not available

Premedication Protocol for Rituximab

When using IV/IM diphenhydramine instead of oral administration, the complete premedication regimen should include:

1. Antihistamine: IV/IM diphenhydramine 25-50 mg
2. Antipyretic: Acetaminophen 650 mg (oral)
3. Corticosteroid: Consider adding IV methylprednisolone (2-40 mg) or hydrocortisone (100 mg) for patients with history of moderate to severe reactions 1

Alternative H1-Antihistamines

If diphenhydramine cannot be used due to contraindications:

• IV cetirizine: Evidence suggests it may be a viable substitute for diphenhydramine in preventing infusion reactions with rituximab 2
• IV promethazine: 12.5-25 mg can be used as an alternative first-generation antihistamine

Evidence-Based Considerations

Efficacy

• Premedication with antihistamines and glucocorticoids has been shown to reduce rituximab infusion-related reactions in patients with B-cell malignancies (2.7% vs 13% without premedication) 1
• The Jung et al. study demonstrated a significant reduction in rituximab infusion-related reactions with glucocorticoid premedication (OR 0.183; 95% CI 0.067-0.496; p<0.001) 1

Important Cautions

• Rapid development of profound hypotension can occur within minutes of rituximab infusion, even with appropriate premedication 3
• Monitor vital signs every 30 minutes initially during infusion, then hourly for at least 4-6 hours 4
• Have emergency medications and equipment readily available for treating potential severe reactions

Advanced Premedication Options

For patients with history of previous reactions or high risk of reactions:

• Enhanced regimen: Consider adding montelukast and rupatadine (second-generation H1-antihistamine) to standard premedication, which has been shown to decrease infusion time, rate and severity of reactions, and use of rescue medications 5
• This combination reduced rituximab infusion reaction rates from 75% with standard premedication to 22% with the enhanced regimen 5

Administration Considerations

• For first-time rituximab administration, start infusion at a slow rate (50 mg/hr) and gradually increase if tolerated 3
• For subsequent infusions in patients who tolerated the first infusion well, a 90-minute rapid infusion protocol may be considered 6
• Always have resuscitation equipment and medications readily available during infusion

Treatment of Infusion Reactions

If a reaction occurs despite premedication:

• Stop the infusion immediately
• Assess vital signs
• Administer additional IV diphenhydramine, corticosteroids, and epinephrine as needed based on severity
• Consider rechallenge at a lower infusion rate (25 mg/hr) after symptoms resolve 3

Remember that while antihistamine premedication is important, the combination with corticosteroids provides the most effective prophylaxis against rituximab infusion reactions, particularly in patients with B-cell malignancies.