Are Doxepin and Adarax (Loratadine) in the Same Drug Class?
No, doxepin and loratadine (Adarax) are not in the same drug class. Doxepin is a tricyclic antidepressant with potent antihistamine properties, while loratadine is a second-generation non-sedating antihistamine. 1, 2
Drug Classification
Doxepin
- Primary class: Tricyclic antidepressant (TCA) 3, 1
- Chemical structure: Closely related to other TCAs such as amitriptyline and imipramine 1
- Mechanism: At therapeutic antidepressant doses (typically 75-300 mg/day), it functions as a TCA with mood-elevating and sedative effects 1
- At low doses (1-6 mg): Functions primarily as a potent H1-histamine receptor antagonist with unique selectivity for this receptor 4
- Additional properties: Also possesses H2-blocking activity, which distinguishes it from conventional antihistamines 5
Loratadine (Adarax)
- Primary class: Second-generation non-sedating antihistamine 2
- Chemical structure: Related to tricyclic antidepressants structurally, but functions entirely differently 2
- Mechanism: Selective peripheral H1-receptor antagonist with threefold greater affinity for peripheral versus central histamine receptors 2
- Key characteristic: Minimal CNS penetration, resulting in non-sedating properties 2
Clinical Distinctions
Sedation Profile
- Doxepin: Causes significant sedation even at low doses due to CNS penetration; this is a primary therapeutic effect when used for insomnia 3, 4
- Loratadine: Produces sedation no more frequently than placebo due to minimal brain penetration 2
Duration and Dosing
- Doxepin: Typically dosed 10 mg three times daily for pruritus, or 1-6 mg once nightly for insomnia 3, 5
- Loratadine: Once-daily dosing with onset within 1 hour and duration of at least 24 hours 2
Therapeutic Applications
- Doxepin: Used for depression (at high doses), insomnia (at low doses 1-6 mg), chronic urticaria refractory to conventional antihistamines, and pruritus associated with various conditions 3, 6, 5
- Loratadine: Used for allergic rhinitis, urticaria, and acute allergic reactions 3, 2
Important Clinical Caveats
When Doxepin May Be Preferred Over Conventional Antihistamines
- Chronic urticaria poorly responsive to standard antihistamines: Doxepin 10 mg three times daily shows complete response in 44% and overall response in 75% of refractory cases 6
- The superior efficacy may be due to combined H1 and H2 blocking properties that conventional antihistamines lack 5
Safety Considerations
- Doxepin carries TCA-related risks: Including cardiotoxicity on overdose, anticholinergic effects (dry mouth, constipation), and potential for drug interactions as a sodium channel blocker 3, 1
- Topical doxepin: Should be limited to 8 days, 10% of body surface area, and 12 g daily due to systemic absorption and sedation risk 3
- Loratadine: Has minimal adverse effects comparable to placebo, with no significant drug interaction potential 2
Common Pitfall
Do not assume that because loratadine is "chemically related to tricyclic antidepressants" 2 that it shares their pharmacologic class or clinical properties—the structural similarity does not translate to functional similarity, as loratadine lacks antidepressant, anticholinergic, and sodium channel blocking effects.