SEMPREX-D
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEMPREX-D (SEMPREX-D).
SEMPREX-D combines acrivastine, a histamine H1 receptor antagonist, and pseudoephedrine, a sympathomimetic amine vasoconstrictor. Acrivastine blocks peripheral histamine-mediated effects, while pseudoephedrine constricts nasal blood vessels to reduce congestion.
| Metabolism | Acrivastine: Partially metabolized by carboxylesterases and CYP450 isozymes (minor). Pseudoephedrine: Minimally metabolized by N-demethylation in the liver. |
| Excretion | Renal (approx. 60% as unchanged drug and metabolites), biliary/fecal (approx. 40%). |
| Half-life | Terminal elimination half-life is approximately 8-12 hours, allowing twice-daily dosing. |
| Protein binding | Approximately 85% bound to plasma proteins, mainly albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent Vd is about 3-4 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability of pseudoephedrine is about 100%; brompheniramine is approximately 50-70% due to first-pass metabolism. |
| Onset of Action | Oral: 15-30 minutes for decongestant effect; antihistamine effect begins within 1 hour. |
| Duration of Action | Decongestant effect lasts up to 12 hours; antihistamine effect persists for approximately 12-24 hours, supporting twice-daily administration. |
| Molecular Weight | Pseudoephedrine: 165.23 Da; Carbinoxamine: 290.79 Da |
1 capsule orally every 12 hours; each capsule contains acrivastine 8 mg and pseudoephedrine 60 mg.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated in severe renal impairment (GFR <30 mL/min). For GFR 30-50 mL/min: reduce frequency to every 24 hours. For GFR >50 mL/min: no adjustment needed. |
| Liver impairment | Avoid use in severe hepatic impairment (Child-Pugh class C). For Child-Pugh class A or B: use with caution, no specific dose adjustment recommended; monitor for adverse effects. |
| Pediatric use | Not recommended for children under 12 years. For children ≥12 years: same as adult dosing (1 capsule every 12 hours). |
| Geriatric use | Use with caution; may be more sensitive to anticholinergic and sympathomimetic effects. Consider starting with lower dose or extended dosing interval. Avoid in patients with significant cardiovascular disease, hypertension, or prostatic hyperplasia. |
| 1st trimester | Contains pseudoephedrine and carbinoxamine. Pseudoephedrine may be associated with gastroschisis in first trimester; avoid. Carbinoxamine is a first-generation antihistamine; limited data suggest low risk but avoid due to potential teratogenic effects of sympathomimetics. |
| 2nd trimester | Pseudoephedrine may cause uterine artery constriction; use only if clearly needed. Carbinoxamine generally considered safe but drowsiness may affect mother. |
| 3rd trimester | Pseudoephedrine may cause uterine artery constriction and fetal tachycardia; avoid near term. Carbinoxamine is safe but may cause neonatal irritability or sedation if used near delivery. |
Clinical note
Comprehensive clinical and safety monograph for SEMPREX-D (SEMPREX-D).
| Placental transfer | Both pseudoephedrine and carbinoxamine cross the placenta. Pseudoephedrine achieves fetal plasma levels similar to maternal; carbinoxamine transfer is less well studied but expected due to low molecular weight. |
| Breastfeeding |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to pseudoephedrine, carbinoxamine, or any componentSevere hypertension or coronary artery diseaseNarrow-angle glaucomaUrinary retentionConcurrent use of MAO inhibitors or within 14 daysSevere hepatic or renal impairment
| Precautions | Cardiovascular effects: Pseudoephedrine may cause hypertension, palpitations, and arrhythmias., CNS stimulation: Insomnia, nervousness, dizziness, or tremors., Urinary retention: Caution in patients with prostatic hypertrophy., Increased intraocular pressure: Avoid in narrow-angle glaucoma., Severe hepatic or renal impairment: Use with caution., Hypertension: Contraindicated in severe hypertension or coronary artery disease. |
| Food/Dietary | Avoid high-tyramine foods (aged cheese, cured meats, fermented products) with pseudoephedrine due to risk of hypertensive crisis. Caffeine may exacerbate CNS stimulation. Grapefruit juice may decrease pseudoephedrine absorption. |
Loading safety data…
| Pseudoephedrine is excreted into breast milk in small amounts; may cause irritability in infants. Carbinoxamine is excreted in low levels; may cause sedation. Use with caution and monitor infant for drowsiness, irritability, or feeding difficulties. Avoid in premature or neonatal infants. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | No adequate studies in pregnant women. First trimester: known fetal risks associated with sympathomimetics (e.g., reduced uteroplacental blood flow, potential for neural tube defects at high doses). Second trimester: possible association with gastroschisis from pseudoephedrine. Third trimester: risk of preterm labor, fetal tachycardia, and intrauterine growth restriction due to vasoconstriction. Avoid use during pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and fetal heart rate. Assess for signs of preterm labor. Consider fetal growth ultrasound if used long-term. Evaluate for maternal CNS stimulation or cardiovascular adverse effects. |
| Fertility Effects | Limited data. Sympathomimetics may theoretically impair uterine blood flow and ovulatory function. No established effect on female or male fertility. Use not recommended in patients attempting conception without medical guidance. |
| Clinical Pearls | SEMPREX-D (acrivastine + pseudoephedrine) is a combination antihistamine and decongestant. Acrivastine is a second-generation antihistamine with a rapid onset of action (15-30 minutes) and short half-life (~1.5 hours). Pseudoephedrine is a sympathomimetic amine. Avoid in patients with severe hypertension, coronary artery disease, or MAO inhibitor use within 14 days. Caution in hyperthyroidism, diabetes, and prostatic hypertrophy. Monitor for CNS stimulation, insomnia, and increased blood pressure. |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose. · Do not take within 14 days of MAO inhibitors. · Avoid alcohol and other CNS depressants. · May cause dizziness or drowsiness; use caution when driving. · Report chest pain, palpitations, difficulty urinating, or severe nervousness. · Do not crush or chew sustained-release formulations. |