Antihistamines
- H1-antihistamines primarily used in dermatology
1st generation
- Diphenhydramine (Pregnancy category B)
- Chlorpheniramine (Pregnancy category B)
- Cyproheptadine (Pregnancy category B)
- Promethazine (Pregnancy category C)
- Hydroxyzine (Pregnancy category C)
2nd generation
- Mizolastine
- Loratadine (Pregnancy category B)
- Desloratadine (Pregnancy category C)
- Cetirizine (Pregnancy category B)
- Levocetirizine (Pregnancy category B)
- Fexofenadine (Pregnancy category C)
- Rupatadine
- Bilastine (limited data for use during pregnancy)
Others
- H2 antihistamines: Ranitidine & Cimetidine
- Tricyclic antidepressant with anti-H1 & H2 activity: Doxepin (Pregnancy category C)
- Dose 10-25mg orally every night at bedtime
1st generation
- Metabolized by CYP3A4 (1/2 life can be prolonged in cases of liver disease/use of CYP3A4 inhibitors)
- Lipophilic (cross blood-brain barrier)
- Renally excreted (Diphenhydramine – minimal)
2nd generation
- Metabolized by CYP3A4 (Fexofenadine & Desloratadine not metabolized by CYP3A4)
- Less lipophilic (↓ability to cross blood-brain barrier)
- Loratadine & Cetirizine: dose adjustment needed in hepatic/renal impairment e.g. Cetirizine 5mg instead of 10mg
Doxepin
- Metabolism via CYP2D6
- Antagonists of histamine at histamine receptors + inverse agonists (downregulate histamine receptors)
- Released histamine: mediates itch, causes vasodilation & increased vascular permeability
- Urticaria & angioedema
- 1st generation antihistamines helpful for itching at night (sedative effect)
- Cyproheptadine: Cold urticaria, anorexia nervosa (interferes with hypothalamic function leading to increased appetite & weight gain)
- Doxepin: Urticaria, acne excoriee, neurotic excoriations
1st & 2nd generation
- Hypersensitivity
- Severe hepatic or renal impairment
1st generation
- Angle closure glaucoma
- Lactation
- Newborns/ premature infants
Doxepin
- In combination with other antidepressants
- Severe cardiac disease (risk of QT prolongation)
- Narrow angle glaucoma
- Urinary retention
- Monoamine oxidase inhibitors, within last 14 days
1st generation
- Sedation
- Impaired cognitive function
- Anticholinergic side effects (dry mouth, dry eyes, blurred vision, constipation, urinary retention, increased ocular pressure, glaucoma)
- Hyperexcitability (in children if given in high doses)
- Growth retardation in children with Cyproheptadine (in high doses)
2nd generation
- Less sedating (cetirizine most sedating of all; 10% of patients)
- No anticholinergic side effects
Doxepin
- Sedation
- Anticholinergic SE
- Orthostatic hypotension
- Decreases seizure threshold
- Induction of manic episode (patients known for manic depressive disorder)
- Suicidality (black box warning)
1st generation
- Through CYP3A4 inhibitors (Macrolide antibiotics, Azole antifungals, HIV protease inhibitors, SSRI antidepressants, foods e.g. grapefruit juice)
- Note: Cimetidine is a CYP3A4 inhibitor
1st generation
- Give every night at bedtime (sedative effect)
- Onset of action may take > an hour
Notes
- Desloratadine (active metabolite of Loratadine): 5x more potent than Loratadine in suppressing wheals
- Diphenhydramine & Chlorpheniramine are safest during 1st trimester, & during lactation (although better avoided in lactation, due to risk of neonatal sedation)
- Loratadine then Cetirizine are considered safest during the last trimesters of pregnancy
- Doxepin: Higher affinity for histamine receptor than others + longer therapeutic effect due to longer 1/2 life
- Doxepin also available in topical preparation (Pregnancy category B). SE include drowsiness, & sensitization (risk of systemic allergic contact dermatitis to oral doxepin)