ALLEGRA-D 12 HOUR ALLERGY AND CONGESTION
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALLEGRA-D 12 HOUR ALLERGY AND CONGESTION (ALLEGRA-D 12 HOUR ALLERGY AND CONGESTION).
Fexofenadine is a selective peripheral H1-receptor antagonist; pseudoephedrine is a sympathomimetic amine that directly stimulates alpha-adrenergic receptors, causing vasoconstriction and decongestion.
| Metabolism | Fexofenadine is minimally metabolized by the liver (≤5% via CYP3A4); pseudoephedrine is partially metabolized by hepatic N-demethylation and undergoes renal excretion. |
| Excretion | Fexofenadine: 95% excreted unchanged in feces (biliary) and 5% in urine. Pseudoephedrine: 90% excreted unchanged in urine; remainder undergoes hepatic N-demethylation. |
| Half-life | Fexofenadine: 14.4 hours in healthy adults (range 11-15 h); pseudoephedrine: 5-8 hours (pH-dependent urinary excretion may prolong to 14-16 h in alkaline urine). |
| Protein binding | Fexofenadine: 60-70% bound to plasma proteins (albumin and α1-acid glycoprotein). Pseudoephedrine: negligible binding (<5%). |
| Volume of Distribution | Fexofenadine: 3.3 L/kg (large Vd, extensive tissue distribution); pseudoephedrine: 2.6-3.5 L/kg (distributes into body water). |
| Bioavailability | Fexofenadine: 33% oral bioavailability (first-pass effect minimal, but absorption incomplete). Pseudoephedrine: ~90% oral bioavailability. |
| Onset of Action | Fexofenadine: 1-2 hours (oral); pseudoephedrine: 30 minutes (oral) for nasal decongestion. |
| Duration of Action | Fexofenadine: 24 hours (antihistamine effect); pseudoephedrine: 4-6 hours (decongestant) but extended-release formulation provides 12-hour coverage. |
| Molecular Weight | Fexofenadine: 501.53 Da; Pseudoephedrine: 165.23 Da |
Adults and children 12 years and older: 1 tablet (fexofenadine 60 mg/pseudoephedrine 120 mg) orally every 12 hours with water. Do not exceed 2 tablets in 24 hours.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | Contraindicated in severe renal impairment (CrCl < 30 mL/min). For mild to moderate impairment (CrCl 30-80 mL/min): fexofenadine dose adjustment recommended (not to exceed 60 mg once daily), but pseudoephedrine accumulation may occur; use alternative product. Not studied in ESRD. |
| Liver impairment | No dosage adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); caution. |
| Pediatric use | Children under 12 years: not recommended. For children ≥12 years: same as adult dosing: 1 tablet every 12 hours with water. |
| Geriatric use | Elderly patients may be more sensitive to CNS effects and anticholinergic effects of pseudoephedrine. Not recommended due to increased risk of adverse reactions; consider alternative therapy. If used, monitor closely. |
| 1st trimester | Avoid due to potential teratogenic effects (fexofenadine is category C; pseudoephedrine associated with gastroschisis in first trimester). |
| 2nd trimester | Use only if clearly needed; pseudoephedrine may cause uterine artery vasoconstriction. |
| 3rd trimester | Avoid near term; pseudoephedrine can cause uterine irritability and neonatal tachycardia. |
Clinical note
Comprehensive clinical and safety monograph for ALLEGRA-D 12 HOUR ALLERGY AND CONGESTION (ALLEGRA-D 12 HOUR ALLERGY AND CONGESTION).
| Placental transfer | Pseudoephedrine crosses placenta; fexofenadine likely crosses but to lesser extent. Evidence limited. |
| Breastfeeding | Fexofenadine is excreted in low levels; pseudoephedrine is concentrated in breast milk and may cause irritability or drowsiness in infants. Use caution. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to fexofenadine, pseudoephedrine, or any componentSevere hypertensionCoronary artery diseaseUse of MAOIs within 14 daysNarrow-angle glaucomaUrinary retentionSevere renal impairment
| Precautions | Cardiovascular effects: hypertension, arrhythmias, palpitations, tachycardia, myocardial infarction, stroke (especially with pre-existing cardiovascular disease or concomitant use with other sympathomimetics)., Central nervous system stimulation: nervousness, dizziness, insomnia, tremor, seizures (may be exacerbated in patients with seizure disorders)., Increased intraocular pressure: contraindicated in narrow-angle glaucoma., Urinary retention: use with caution in patients with prostate hypertrophy or obstructive uropathy., Thyroid disorders: may aggravate hyperthyroidism; use with caution., Diabetes mellitus: may increase blood glucose; monitor in diabetic patients., Acute allergic reactions: discontinue if severe hypersensitivity occurs., Renal impairment: fexofenadine clearance reduced; avoid use in severe renal impairment (CrCl <30 mL/min)., Elderly: more sensitive to adverse effects; use with caution., Drug interactions: MAO inhibitors (hypertensive crisis); antihypertensives (reduced effect); alcohol/CNS depressants (additive effects). |
Loading safety data…
| Lactation Rating |
| L4 (Possibly Hazardous) – pseudoephedrine component |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Animal studies show teratogenic effects at high doses of fexofenadine; pseudoephedrine may cause reduced uterine blood flow. Second and third trimesters: Risk of uterine contractions and fetal hypoxia due to pseudoephedrine vasoconstriction; avoid in preeclampsia. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate; fetal heart rate monitoring if prolonged use; assess for signs of uterine hyperstimulation. |
| Fertility Effects | No known adverse effects on fertility in humans; animal studies showed no impairment with fexofenadine or pseudoephedrine. |
| Food/Dietary | Avoid alcohol, which can increase drowsiness. Grapefruit juice may reduce absorption of fexofenadine; avoid concurrent intake. Taking with high-fat meal may slow absorption but not affect overall efficacy. |
| Clinical Pearls | Allegra-D 12 Hour contains fexofenadine (antihistamine) and pseudoephedrine (decongestant). Pseudoephedrine can cause insomnia, so advise taking the last dose early in the evening. Avoid in patients with severe hypertension, coronary artery disease, or narrow-angle glaucoma. Use with caution in hyperthyroidism, diabetes, and prostatic hypertrophy. Do not exceed recommended dose; extended-release formulation must be swallowed whole. |
| Patient Advice | Take this medication by mouth with or without food, usually every 12 hours. · Swallow the tablet whole; do not crush, chew, or break it. · Do not take more than 2 tablets in 24 hours. · Avoid taking at bedtime to prevent difficulty sleeping. · Do not take with other products containing pseudoephedrine or other decongestants. · Stop use and ask a doctor if symptoms do not improve within 7 days or are accompanied by fever. · Keep out of reach of children. |