Non-sedating Antihistamines

Last Updated

Medications listed in the tables and non-FDA approved indications included in these retrospective criteria are not indicative of Texas Vendor Drug Program formulary coverage.

  • Revision history
    • July 2022, June 2020; June 2018; July 2016; May 2016; Sept. 2014; Dec. 2012; March 2011; Feb. 2011; Jan. 2011; Jan. 2008; April 2003: April 2002; April 2001; April 2000; March 1999; March 1998; Aug. 1997. 
  • Initially developed
    • March 1997

1. Dosage

Oral non-sedating antihistamines are FDA-approved for managing urticaria and allergic rhinitis. Nasal non-sedating antihistamines as monotherapy and combination therapy are FDA-approved for treating allergic rhinitis and vasomotor rhinitis. The oral non-sedating antihistamines desloratadine and acrivastine are available only by prescription. Inhalational non-sedative antihistamines are also available; olopatadine (Patanase®) and azelastine (Astepro®) are available by prescription and azelastine (Astepro Allergy ®) are available now over the counter.

1.1. Adults

Maximum recommended daily dosages for available non-sedating antihistamines are summarized in Tables 1 and 2. Dosages identified in Texas Medicaid patient profiles exceeding these recommendations will be reviewed.

Table 1. Adult Maximum Recommended Daily Dosages for Non-sedating Antihistamines – Monotherapy 1-12
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage 
azelastine (Astepro®, Astepro Allergy®, generics) **0.15% nasal solution – 205.5 mcg/spray seasonal or perennial allergic rhinitis 2 sprays per nostril twice daily
azelastine (generics) 0.1% nasal solution – 137 mcg/spray perennial allergic rhinitis 2 sprays per nostril twice daily
azelastine (Astepro®, generics)       seasonal allergic rhinitis 2 sprays per nostril twice daily
azelastine (generics)   vasomotor rhinitis 2 sprays per nostril twice daily
cetirizine (Zyrtec®, generics)

**tablets, chewable tablets – 5 mg, 10 mg

**orally disintegrating tablets - 10 mg

**liquid filled capsule – 10 mg

**solution – 1 mg/mL

syrup – 1 mg/ mL

 perennial or seasonal allergic rhinitis 10 mg once daily
cetirizine (Zyrtec®, generics)

**liquid filled capsule – 10 mg

**solution – 1 mg/mL

syrup – 1 mg/mL

**tablets, chewable tablets – 5 mg, 10 mg

 chronic idiopathic urticaria 10 mg once daily
desloratadine (Clarinex®, generics)

tablets – 5 mg

rapidly disintegrating tablets - 2.5 mg, 5 mg

 chronic idiopathic urticaria 5 mg once daily
desloratadine (Clarinex®, generics)   perennial or seasonal allergic rhinitis 5 mg once daily
fexofenadine (Allegra®, generics, Allegra® ODT)

**tablets – 30 mg, 60 mg, 180 mg

**orally disintegrating tablets - 30 mg

**suspension – 30 mg/5 mL

 allergic rhinitis 60 mg twice daily or 180 mg once daily
fexofenadine (Allegra®, generics, Allegra® ODT)   chronic idiopathic urticaria 60 mg twice daily or 180 mg once daily
levocetirizine (Xyzal®, generics)

**tablet – 5 mg

**oral solution – 2.5 mg/5 mL

 allergic rhinitis 5 mg once daily in evening
levocetirizine (Xyzal®, generics)   chronic idiopathic urticaria 5 mg once daily in evening
loratadine (Claritin®, Alavert®, Claritin Children’s®, Claritin RediTabs®, generics)

**tablets – 10 mg

**chewable tablets (Claritin Children’s®) – 5 mg

**rapidly disintegrating tablets (Claritin RediTabs®, Alavert®) 10 mg

**liquid-gel capsule – 10 mg

**solution – 5 mg/5 mL

 perennial or seasonal allergic rhinitis     10 mg once daily
loratadine (Claritin®, Alavert®, Claritin Children’s®, Claritin RediTabs®, generics)   chronic idiopathic urticaria 10 mg once daily
olopatadine (Patanase®, generics) 0.6% nasal solution seasonal allergic rhinitis 2 sprays per nostril twice daily

Legend:

  • **now over-the-counter
  • ODT = orally disintegrating tablet
Table 2. Adult Maximum Recommended Daily Dosages for Non-sedating Antihistamines - Combination Therapy1,2,12-19
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage
azelastine/fluticasone (Dymista®, generics) nasal suspension – 137 mcg/ 50 mcg per actuation seasonal allergic rhinitis 1 spray per nostril twice daily
**cetirizine/ pseudoephedrine (Zyrtec-D®, generics) 12-hour tablets (cetirizine 5 mg/ pseudoephedrine 120 mg/ tablet) perennial or seasonal allergic rhinitis 1 tablet twice daily
**fexofenadine/ pseudoephedrine (Allegra-D®, generics) 12-hour tablets (fexofenadine 60 mg/ pseudoephedrine 120 mg/ tablet) seasonal allergic rhinitis 1 tablet twice daily
**fexofenadine/ pseudoephedrine (Allegra-D®, generics) 24-hour tablets (fexofenadine 180 mg/ pseudoephedrine 240 mg/ tablet) seasonal allergic rhinitis 1 tablet once daily
desloratadine/ pseudoephedrine (Clarinex-D® 12 hour, generics) 12-hour tablets (2.5 mg desloratadine/ 120 mg pseudoephedrine/ tablet seasonal allergic rhinitis 1 tablet twice daily
**loratadine/ pseudoephedrine (Claritin D® 12 Hour, Alavert-D®, generics) 12-hour tablets (loratadine 5 mg/ pseudoephedrine 120 mg/ tablet) seasonal allergic rhinitis 1 tablet twice daily
**loratadine/pseudoephedrine extended-release (Claritin D® 24 Hour, generics) 24-hour tablets (loratadine 10 mg/pseudoephedrine 240 mg/tablet) seasonal allergic rhinitis 1 tablet once daily

Legend:

  • **now over-the-counter

1.2. Pediatrics

Oral non-sedating antihistamines are FDA-approved for use in pediatric patients for allergic rhinitis and chronic urticaria. Cetirizine and levocetirizine are FDA-approved for use in children 6 months of age and older with urticaria and seasonal allergic rhinitis. Desloratadine is FDA-approved for use in children 6 months of age and older with chronic idiopathic urticaria and perennial allergic rhinitis and 2 years of age and older for seasonal allergic rhinitis, and fexofenadine and loratadine are FDA-approved for use in children 2 years and older for allergic rhinitis. The nasal non-sedating antihistamine, azelastine 0.1% solution, is FDA-approved for use in children 2 years and older for seasonal allergic rhinitis treatment, while olopatadine, another nasal non-sedating antihistamine, is indicated for use in children 6 years and older for seasonal allergic rhinitis therapy. Azelastine 0.15% solution is approved for use in children 5 years and older for perennial allergic rhinitis; azelastine 0.1% is FDA-approved for perennial allergic rhinitis treatment in children 6 months to 11 years. Azelastine 0.1% solution is also indicated for use in pediatric patients 12 years and older with vasomotor rhinitis. Safety and efficacy of oral non-sedating antihistamine/decongestant combination products have not been established in children less than 12 years of age. Maximum recommended pediatric dosages for available non-sedating antihistamines are summarized in Tables 3 and 4. Dosages identified in Texas Medicaid patients exceeding these recommendations will be reviewed.

Table 3. Pediatric Maximum Recommended Dosages for Non-sedating Antihistamines – Monotherapy1-11
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage
azelastine (Astepro®, Astepro Allergy®, generics)
  • **0.15% nasal solution – 205.5 mcg/spray
 seasonal and perennial allergic rhinitis
  • 6 years to 11 years:
    • 1 spray per nostril twice daily
  • 12 years to 17 years:
    • 2 sprays per nostril twice daily
azelastine (Astepro ® generics)
  • 0.1% nasal solution – 137 mcg/spray
 perennial allergic rhinitis
  • 6 months to 11 years:
    • 1 spray per nostril twice daily
azelastine (Astepro ® generics)   seasonal allergic rhinitis
  • 2 years to 11 years:
    • 1 spray per nostril twice daily
  • 12 years to 17 years:
    • 2 sprays per nostril twice daily
azelastine (generics)   vasomotor rhinitis
  • 12 years to 17 years:
    • 2 sprays per nostril twice daily
cetirizine (Zyrtec®, generics)
  • **tablets, chewable tablets – 5 mg, 10 mg
  • **orally disintegrating tablets - 10 mg
  • **liquid filled capsule – 10 mg
  • **solution – 1 mg/mL
  • syrup – 1 mg/ mL
 perennial or seasonal allergic rhinitis    
  • 6 months to 11 months:
    • 2.5 mg once daily (oral solution only)
  • 12 months to 5 years:
    • 5 mg once daily
  • 6 years to 17 years:
    • 10 mg once daily
cetirizine (Zyrtec®, generics)
  • **tablets, chewable tablets – 5 mg, 10 mg
  • **liquid filled capsule – 10 mg
  • **solution – 1 mg/mL
  • syrup – 1 mg/ mL
 chronic urticaria
  • 6 months to 11 months:
    • 2.5 mg once daily (oral solution only)
  • 12 months to 5 years:
    • 5 mg once daily
  • 6 years to 17 years:
    • 10 mg once daily
desloratadine (Clarinex®, generics)
  • tablets – 5 mg
  • rapidly disintegrating tablets - 2.5 mg, 5 mg
 chronic idiopathic urticaria; seasonal and perennial allergic rhinitis    
  • 6 years to 11 years:
    • 2.5 mg once daily
  • 12 years to 17 years:
    • 5 mg once daily
fexofenadine (Children’s Allegra® Allergy suspension, generics)
  • **suspension – 30 mg/5 mL
 allergic rhinitis
  • 2 years to 11 years:
    • 30 mg (1 teaspoon) every 12 hours
  • 12 years to 17 years:
    • 60 mg twice daily
fexofenadine (Children’s Allegra® Allergy suspension, generics)
  • **suspension – 30 mg/5 mL
 allergic rhinitis
  • 2 years to 11 years:
    • 30 mg (1 teaspoon) every 12 hours
  • 12 years to 17 years:
    • 60 mg twice daily
fexofenadine (Children’s Allegra® Allergy suspension, generics)   chronic idiopathic urticaria
  • 6 months to 2 years:
    • 15 mg twice daily
  • 2 years to 11 years:
    • 30 mg twice daily
  • 12 years to 17 years:
    • 60 mg twice daily or 180 mg once daily
fexofenadine (Children’s Allegra® Allergy ODT, generics)
  • **orally disintegrating tablets - 30 mg
 allergic rhinitis
  • 6 years to 11 years:
    • 30 mg (1 ODT) on tongue every 12 hours
  • 12 years to 17 years:
    • 60 mg (2 ODTs) on tongue every 12 hours
fexofenadine (Children’s Allegra® Allergy ODT, generics)   chronic idiopathic urticaria
  • 6 years to 11 years:
    • 30 mg (1 ODT) on tongue every 12 hours
  • 12 years to 17 years:
    • 60 mg (2 ODTs) on tongue every 12 hours
fexofenadine (Allegra®, generics)
  • **tablets – 30 mg, 60 mg, 180 mg
 allergic rhinitis
  • 12 years to 17 years:
    • 60 mg twice daily or 180 mg once daily
fexofenadine (Allegra®, generics)   chronic idiopathic urticaria
  • 6 years to 11 years:
    • 30 mg twice daily
  • 12 years to 17 years:
    • 60 mg twice daily or 180 mg once daily
levocetirizine (Xyzal®, generics)
  • **tablet – 5 mg
  • **oral solution – 2.5 mg/5 mL
 allergic rhinitis
  • 6 months to 5 years:*
    • 1.25 mg once daily in the evening (oral solution only)
  • 6 years to 11 years:
    • 2.5 mg once daily in evening
  • 12 years to 17 years:
    • 5 mg once daily in evening
levocetirizine (Xyzal®, generics)   chronic idiopathic urticaria
  • 6 months to 5 years:*
    • 1.25 mg once daily in the evening (oral solution only)
  • 6 years to 11 years:
    • 2.5 mg once daily in evening
  • 12 years to 17 years:
    • 5 mg once daily in evening
loratadine (Claritin®, Alavert®, Claritin Children’s®, Claritin RediTabs®, generics)
  • **tablets – 10 mg
  • **chewable tablets (Claritin®) – 5 mg
  • **rapidly disintegrating tablets (Claritin RediTabs®) – 5 mg, 10 mg
  • **liquid-gel capsule – 10 mg
  • **solution - 5 mg/5 mL
 perennial or seasonal allergic rhinitis
  • 2 years to 5 years:
    • 5 mg once daily (chewable tablets, solution)
  • 6 years to 17 years:
    • 10 mg once daily or 5 mg every 12 hours
  loratadine oral solution 5mg/5mL chronic idiopathic urticaria
  • 6 years to 17 years:
    • 10 mg once daily or 5 mg every 12 hours
olopatadine (Patanase®, generics) 0.6% nasal solution seasonal allergic rhinitis
  • 6 years to 11 years:
    • 1 spray per nostril twice daily
  • 12 years to 17 years:
    • 2 sprays per nostril twice daily

Legend:

  • **now over-the-counter
  • *OTC use only indicated in patients 2 years and older
Table 4. Pediatric Maximum Recommended Dosages for Non-sedating Antihistamines – Combination Therapy1,2,12-19
Drug Name Treatment Indication Dosage Form/Strength Maximum Recommended Dosage
azelastine/fluticasone (Dymista®) seasonal allergic rhinitis nasal suspension – 137 mcg/ 50 mcg per actuation
  • 6 years to 17 years:
    • 1 spray per nostril twice daily
**cetirizine/ pseudoephedrine (Zyrtec-D®, generics) perennial or seasonal allergic rhinitis 12-hour tablets (cetirizine 5 mg/ pseudoephedrine 120 mg/ tablet)
  • 12 years to 17 years:
    • 1 tablet twice daily
**fexofenadine/ pseudoephedrine (Allegra-D®, generics) seasonal allergic rhinitis 12-hour tablets (fexofenadine 60 mg/ pseudoephedrine 120 mg/ tablet)
  • 12 years to 17 years:
    • 1 tablet twice daily
**fexofenadine/ pseudoephedrine (Allegra-D®, generics) seasonal allergic rhinitis 24-hour tablets (fexofenadine 180 mg/ pseudoephedrine 240 mg/ tablet)
  • 12 years to 17 years:
    • 1 tablet once daily
desloratadine/ pseudoephedrine (Clarinex-D® 12 hour, generics) seasonal allergic rhinitis 12-hour tablets (2.5 mg desloratadine/ 120 mg pseudoephedrine/ tablet)
  • 12 years to 17 years:
    • 1 tablet twice daily
**loratadine/pseudoephedrine (Claritin D® 12 Hour, Alavert Allergy and Congestion D®- 12 Hour, generics) seasonal allergic rhinitis 12-hour tablets
(loratadine 5mg/pseudoephedrine 120 mg/tablet)
  • 12 years to 17 years:
    • 1 tablet twice daily
**loratadine/pseudoephedrine extended release (Claritin D® 24 Hour, generics) seasonal allergic rhinitis 24-hour tablets (loratadine 10 mg/pseudoephedrine 240 mg/tablet)
  • 12 years to 17 years:
    • 1 tablet once daily

Legend:

  • **now over-the-counter

2. Duration of Therapy

There is no basis for limiting the duration of treatment for non-sedating antihistamines as patients may suffer from symptoms of allergic rhinitis or other chronic allergic conditions continually.

3. Duplicative Therapy

The concurrent use of two or more non-sedating antihistamines is not recommended20-23 . Additional therapeutic benefit is not experienced when several antihistamines are administered in combination1,2. Patient profiles containing concurrent prescriptions for multiple non-sedating antihistamines will be reviewed.

4. Drug-Drug Interactions

Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically significant for non-sedating antihistamines are summarized in Table 5. Only those drug-drug interactions classified as clinical significance level 1/ contraindicated or those considered life-threatening which have not yet been classified will be reviewed.

Table 5. Non-sedating Antihistamine Drug-Drug Interactions1-19, 24, 25
Target Drug Interacting Drug Interaction Recommendation Clinical Significance Level#
fexofenadine antacids adjunctive administration within 15 minutes of each other decreases fexofenadine bioavailability (AUC ↓’d 41%, Cmax ↓’d 43%), may reduce fexofenadine efficacy space administration times Moderate (DrugReax) 3- Moderate (CP)
fexofenadine P-glycoprotein (P-gp) inducers (e.g., rifamycins, carbamazepine, fosamprenavir) co-administration may decrease fexofenadine serum concentrations and reduce fexofenadine efficacy; drugs such as carbamazepine, rifamycins may activate P-gp transport in small intestine (fexofenadine is substrate of this transport) and decrease fexofenadine oral absorption monitor for decreased fexofenadine therapeutic effects 3-moderate (Lexicomp)
fexofenadine P-glycoprotein (P-gp) inhibitors (e.g., etravirine) co-administration may increase fexofenadine serum concentrations, potentially resulting in enhanced pharmacologic and adverse effects monitor for increased fexofenadine pharmacologic effects 3-Minor (CP)
loratadine amiodarone conjunctive administration may result in reduced loratadine metabolism and enhanced loratadine pharmacologic/adverse effects; amiodarone inhibits CYP3A4, loratadine metabolized by CYP3A4; rare reports of QT interval prolongation with drug combination use cautiously together; QT interval monitoring recommended major (DrugReax)

Legend:

  • #CP = Clinical Pharmacology  

5. References

  1. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc; 2022. Available at: http://www.clinicalpharmacology.com. Accessed June 22, 2022.
  2. IBM Micromedex® DRUGDEX® (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com.ezproxy.lib.utexas.edu/ (cited: June 22, 2022). 
  3. Azelastine 0.1% nasal spray package insert. Amneal Pharmaceuticals LLC, December 2019.
  4. Azelastine (Astepro Allergy®) 0.15% HCl nasal spray. Bayer Hlthcare. June 2021.
  5. Azelastine 0.15% nasal spray (Astepro®) package insert. Apotex Corp., September 201.
  6. Levocetirizine tablets package insert. Camber Pharmaceuticals Inc., September 2019.
  7. Desloratadine tablets, RediTabs®, and oral solution (Clarinex®) package insert. Merck & Co., Inc., May 2020.
  8. Olopatadine (Patanase®) package insert. Alcon Laboratories Inc. March 2021.
  9. Claritin®. Available at: http://www.claritin.com. Accessed June 22, 2022.
  10. Zyrtec®. Available at: http://www.zyrtec.com. Accessed June 22, 2022.
  11. Allegra®. Available at: http://www.allegra.com. Accessed June 22, 2022.
  12. Azelastine HCl and fluticasone propionate (Dymista®) nasal spray package insert. Meda Pharmaceuticals Inc. Updated April 2021. 
  13. Cetirizine HCl and pseudoephedrine HCl (Zyrtec-D®) package insert. J and J Consumer Inc. Updated November 2021. 
  14. Fexofenadine HCl and pseudoephedrine HCl (Allegra-D 12 Hour Allergy and Congestion®) package insert. Chattem Sanofi. Updated June 2016. 
  15. Fexofenadine HCl and pseudoephedrine HCl (Allegra-D 24 Hour Allergy and Congestion®) package insert. Chattem Sanofi. Updated June 2016. 
  16. Desloratadine and pseudoephedrine sulfate (Clarinex-D 12 Hour®) package insert. Organon. Updated March 2019.
  17. Loratadine and pseudoephedrine sulfate (Claritin-D 12 hour®) package insert. Bayer Hlthcare. Updated March 2019.
  18. Loratadine and pseudoephedrine sulfate (Claritin-D 24 hour®) package insert. Bayer Hlthcare. Updated July 2018.
  19. Loratadine and pseudoephedrine sulfate (Alavert Allergy Sinus -D®) package insert. Bayer Hlthcare. Updated July 2018.
  20. Sur DK, Scandale S. Treatment of allergic rhinitis. Am Fam Physician. 2010; 81(12):1440-6.
  21. Kaliner MA. A novel and effective approach to treating rhinitis with nasal antihistamines. Ann Allergy, Asthma, & Immunol. 2007;99:383-90. 
  22. Barr JG, Al-Reefy B, Fox AT, Hopkins C. Allergic rhinitis in children. BMJ. 2014;349:g4153.
  23. Wallace DV, Dykewicz MS, Bernstein DI, et al. for the Joint Task Force on Practice Parameters for Allergy and Immunology. The diagnosis and management of rhinitis: An updated practice parameter. J Allergy Clin Immunol. 2008;122(2)Suppl:S1-S84.
  24. Lexicomp Inc., Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc.; 2022; Accessed June 24, 2022.
  25. Amiodarone (Cordarone®) package insert. Cameron Pharmaceuticals LLC, April 2020.