Can intranasal azelastine (antihistamine) and fluticasone (corticosteroid) be safely used to treat allergic rhinitis during pregnancy?

Azelastine & Fluticasone Nasal Spray Use in Pregnancy

Intranasal fluticasone can be safely used during pregnancy, but azelastine has limited safety data and should be avoided unless no safer alternatives exist. 1

Fluticasone Safety Profile

Fluticasone propionate is considered safe at recommended doses throughout pregnancy based on substantial accumulated safety data alongside budesonide and beclomethasone. 1, 2, 3

• A meta-analysis found no increased risk of major malformations, preterm delivery, low birth weight, or pregnancy-induced hypertension with intranasal corticosteroid use during pregnancy. 1, 2, 3

• Systemic absorption after intranasal administration is markedly lower than oral corticosteroids, supporting a favorable safety profile. 1, 3

• In a controlled study of 53 pregnant women using fluticasone propionate nasal spray, maternal cortisol levels, fetal growth, and pregnancy outcomes were comparable to untreated controls. 3

Clinical Decision Algorithm for Fluticasone

If already using fluticasone before pregnancy:

• Continue the same regimen without interruption using the lowest effective dose. 2, 3
• Switching agents is unnecessary as no meaningful differences in efficacy or safety exist among intranasal corticosteroids. 1, 3

If initiating therapy during pregnancy:

• Intranasal budesonide is preferred as first-line due to FDA Pregnancy Category B classification based on the most extensive human safety data (>6,600 pregnancies). 2, 3
• Fluticasone propionate remains an acceptable alternative at recommended doses. 2, 3

Dosing Strategy

• Use the lowest effective dose that controls symptoms throughout all trimesters. 2, 3
• Do not exceed manufacturer-specified maximum daily dose. 2

Azelastine Safety Concerns

Azelastine has limited safety data in pregnancy and should be used with caution. 1

• The FDA label states azelastine is Pregnancy Category C and has been shown to cause developmental toxicity in animal studies at high doses. 4

• Currently, there are limited data on azelastine use during human pregnancy, with no epidemiologic studies published. 1

• The FDA label advises that azelastine "should be used in pregnancy only if the potential benefit justifies the potential risks to the fetus." 4

Safer Antihistamine Alternatives

First-generation antihistamines (e.g., chlorpheniramine) are preferred over azelastine based on extensive safety data from 200,000 first-trimester exposures showing no increased teratogenic risk. 5, 6

Second-generation oral antihistamines with better safety profiles:

• Loratadine is the most studied second-generation antihistamine (2,147 exposed pregnancies) with no increased risk of major congenital malformations. 6
• Cetirizine has been well-studied and is generally considered safe. 7

Combination Product Considerations

The azelastine-fluticasone combination spray should be avoided during pregnancy due to the limited safety data on azelastine, even though the fluticasone component is considered safe. 1

Recommended Treatment Algorithm

For allergic rhinitis in pregnancy, use this stepwise approach:

1. First-line therapy:

   • Intranasal budesonide (if initiating therapy) 2, 3
   • Continue intranasal fluticasone (if already using pre-pregnancy) 2, 3
   • Intranasal sodium cromolyn 1

2. Add oral antihistamine if needed:

   • First-generation antihistamines (e.g., chlorpheniramine) 5, 6
   • Loratadine or cetirizine as second-generation alternatives 6, 7

3. Avoid:

   • Intranasal azelastine due to limited human data 1
   • Oral decongestants in the first trimester (associated with gastroschisis and intestinal atresia) 1

Critical Pitfalls to Avoid

• Do not confuse intranasal with oral corticosteroids. Oral corticosteroids carry significantly higher risks, especially in the first trimester, including increased risk of cleft lip/palate, preeclampsia, preterm delivery, and gestational diabetes. 2, 3

• Do not unnecessarily discontinue effective intranasal corticosteroid therapy already controlling symptoms before pregnancy, as untreated rhinitis can significantly impact quality of life and potentially worsen comorbid conditions like asthma. 2, 8

• Avoid combining oral decongestants with acetaminophen or salicylates as this increases the risk of congenital malformations. 1

Breastfeeding Compatibility

Intranasal fluticasone is compatible with breastfeeding due to minimal systemic absorption resulting in negligible drug transfer to breast milk. 2