Can You Mix Loratadine (Adarax) and Trazodone?
Yes, loratadine and trazodone can be safely co-administered without significant drug interactions or contraindications.
Safety Profile of the Combination
Loratadine is a second-generation antihistamine that does not cause clinically significant CNS depression and has minimal sedative effects, making it fundamentally different from first-generation antihistamines that would pose additive sedation risks with trazodone 1.
Loratadine does not enter the brain in significant amounts and has threefold greater affinity for peripheral versus central histamine receptors, which explains its lack of sedative properties 2.
There are no documented pharmacokinetic interactions between loratadine and trazodone, as loratadine is metabolized primarily to its active metabolite descarbethoxyloratadine without significant CYP3A4 inhibition that would affect trazodone metabolism 2.
Key Differences from Problematic Antihistamines
Older antihistamines like terfenadine and astemizole were associated with cardiac arrhythmias and QTc prolongation, particularly when combined with CYP3A4 inhibitors, but loratadine does not share these cardiac risks 3.
First-generation antihistamines (diphenhydramine, hydroxyzine) cause significant sedation and would create additive CNS depression with trazodone, but loratadine demonstrated no reduction in sleep latency or performance impairment even at doses up to 40 mg 1.
Clinical Considerations
Monitor for mild additive sedation initially, though this is unlikely given loratadine's minimal CNS penetration, as trazodone's sedative effects are primarily mediated through 5-HT2A, H1, and alpha-1 adrenergic receptor antagonism 4.
No dose adjustments are required for either medication when used together, as loratadine reaches peak concentration in 1-2 hours with a 10-hour half-life and once-daily dosing, while trazodone is typically dosed at bedtime 2, 4.
Patients can take loratadine during the day for allergic symptoms and trazodone at bedtime without concern for significant drug-drug interactions or excessive sedation 3, 5.
Common Pitfall to Avoid
Do not confuse loratadine with first-generation antihistamines like hydroxyzine or diphenhydramine, which would require caution when combined with trazodone due to additive anticholinergic effects and CNS depression 3.