ALLEGRA-D 24 HOUR ALLERGY AND CONGESTION
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALLEGRA-D 24 HOUR ALLERGY AND CONGESTION (ALLEGRA-D 24 HOUR ALLERGY AND CONGESTION).
Fexofenadine is a selective peripheral H1-receptor antagonist that inhibits histamine release from mast cells. Pseudoephedrine is a sympathomimetic amine that directly stimulates alpha-adrenergic receptors in the respiratory tract mucosa, causing vasoconstriction and reducing nasal congestion. It also has weak beta-adrenergic activity.
| Metabolism | Fexofenadine is minimally metabolized (≤5% of dose) by the liver, primarily via CYP3A4; other minor pathways involve CYP2D6 and CYP2C9. Pseudoephedrine is partially metabolized in the liver by N-demethylation (CYP2D6) and oxidative deamination. |
| Excretion | Fexofenadine: ~95% excreted unchanged in feces (80%) and urine (11-12%); pseudoephedrine: ~70-90% excreted unchanged in urine (major route). |
| Half-life | Fexofenadine: terminal half-life 14.4 hours (range 11-17 h, ~4-fold longer than IV due to enterohepatic recirculation); pseudoephedrine: terminal half-life 4.3-8 hours (alkaline urine prolongs to 16 h). |
| Protein binding | Fexofenadine: 60-70% primarily to albumin and α1-acid glycoprotein; pseudoephedrine: negligible protein binding (<20%, mainly to albumin). |
| Volume of Distribution | Fexofenadine: 5.4-5.8 L/kg (extensive tissue distribution, ~30-40 times plasma volume); pseudoephedrine: 2.6-3.5 L/kg (distributes into body water, crosses blood-brain barrier). |
| Bioavailability | Fexofenadine: ~33-40% (oral, decreased by fruit juices); pseudoephedrine: ~85-100% (oral, minimally affected by food). |
| Onset of Action | Fexofenadine: antihistamine effect within 1-2 hours (oral); pseudoephedrine: decongestant effect within 30-60 minutes (oral). |
| Duration of Action | Fexofenadine: 24 hours (symptom relief for seasonal allergies); pseudoephedrine: 4-6 hours per immediate-release component (extended-release formulation provides 24-hour decongestion). |
| Molecular Weight | Fexofenadine: 501.7 Da; Pseudoephedrine: 165.2 Da |
1 tablet (fexofenadine 180 mg / pseudoephedrine 240 mg) orally every 24 hours.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-49 mL/min: 1 tablet every 24 hours; GFR 15-29 mL/min: 1 tablet every 48 hours; GFR <15 mL/min: contraindicated or not recommended. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe impairment (Child-Pugh C); use with caution. |
| Pediatric use | Not recommended for children under 12 years. For age >=12 years: same as adult dosing (1 tablet every 24 hours). |
| Geriatric use | Elderly patients may have reduced renal function; assess renal function prior to use. Initial dose may be adjusted based on renal function. Avoid use in patients with hypertension or cardiovascular disease due to pseudoephedrine. |
| 1st trimester | Avoid. The combination contains pseudoephedrine which may be associated with increased risk of gastroschisis. Fexofenadine is generally considered low risk but data are limited. |
| 2nd trimester | Use with caution. Pseudoephedrine may reduce uteroplacental blood flow; fexofenadine is preferred over first-generation antihistamines. |
| 3rd trimester | Avoid near term. Pseudoephedrine may cause uterine contractions and reduce placental perfusion. Fexofenadine is generally safe but lacks robust data. |
Clinical note
Comprehensive clinical and safety monograph for ALLEGRA-D 24 HOUR ALLERGY AND CONGESTION (ALLEGRA-D 24 HOUR ALLERGY AND CONGESTION).
| Placental transfer | Both fexofenadine and pseudoephedrine cross the placenta. Fexofenadine shows limited transfer (about 10% maternal plasma levels in cord blood). Pseudoephedrine readily crosses with fetal levels approximating maternal levels. |
| Breastfeeding |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to fexofenadine, pseudoephedrine, or any componentSevere hypertensionCoronary artery diseaseUse of monoamine oxidase inhibitors (MAOIs) within 14 daysNarrow-angle glaucomaUrinary retentionSevere hepatic or renal impairment
| Precautions | Cardiovascular effects (hypertension, palpitations, tachycardia, arrhythmias) especially in patients with pre-existing cardiovascular disease; CNS stimulation (insomnia, nervousness, dizziness, anxiety); risk of ischemic colitis; urinary retention (especially in patients with prostatic hypertrophy); increased intraocular pressure in patients with narrow-angle glaucoma; severe hypertension or coronary artery disease; MAOI use or within 14 days of discontinuation; use in renal impairment requires caution; avoid use with alcohol or other CNS depressants; caution in patients with hyperthyroidism, diabetes mellitus, or angle-closure glaucoma; elderly patients may be more sensitive to side effects. |
| Food/Dietary | Fruit juices (apple, orange, grapefruit) significantly reduce fexofenadine absorption; take with water only. Avoid high-fat meals as they may affect pseudoephedrine absorption. No specific restrictions for pseudoephedrine, but avoid excessive caffeine (coffee, tea, cola) to reduce additive stimulant effects. |
Loading safety data…
| Small amounts of fexofenadine and pseudoephedrine are excreted into breast milk. Pseudoephedrine may cause irritability or sedation in infants and can reduce milk supply. Use lowest effective dose for shortest duration. Monitor infant for signs of stimulation or drowsiness. |
| Lactation Rating | L3 - Limited Data (moderately safe; use with caution) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No adequate studies, animal studies show potential risk. Second and third trimesters: Risk unknown; associated with increased risk of gastrointestinal atresia and gastroschisis with first trimester pseudoephedrine use. Avoid in preeclampsia due to vasoconstriction. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate due to pseudoephedrine's sympathomimetic effects. In third trimester, monitor for uterine contractions and fetal heart rate. Assess for signs of placental insufficiency or intrauterine growth restriction. |
| Fertility Effects | Fexofenadine: No known effect on fertility. Pseudoephedrine: May affect fertility due to vasoconstriction reducing uterine blood flow; unclear direct effect on conception. |
| Clinical Pearls | ALLEGRA-D 24 HOUR ALLERGY AND CONGESTION contains fexofenadine 180 mg and pseudoephedrine 240 mg extended-release. Avoid in severe hypertension, coronary artery disease, narrow-angle glaucoma, urinary retention, and concurrent MAOI use or within 14 days. CNS stimulation possible; monitor for insomnia, nervousness, and dizziness. Not recommended in patients with impaired renal function (CrCl < 60 mL/min) due to fexofenadine accumulation. Do not crush or chew tablet. |
| Patient Advice | Take one tablet daily with water; do not crush or chew. · Avoid taking with fruit juices (e.g., apple, orange, grapefruit) as they may decrease absorption. · Do not use with other products containing pseudoephedrine or antihistamines. · Stop and consult doctor if symptoms do not improve within 7 days or are accompanied by fever. · Avoid alcohol and sedatives as they may increase dizziness. · Discontinue if signs of hypertension or tachycardia occur. · Contraindicated within 14 days of stopping MAOIs. · Pregnant or nursing women should consult a physician before use. |