ACTIFED
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACTIFED (ACTIFED).
ACTIFED contains triprolidine, a first-generation antihistamine that competitively inhibits histamine H1 receptors, and pseudoephedrine, a sympathomimetic amine that directly stimulates alpha-adrenergic receptors, causing vasoconstriction and decongestion.
| Metabolism | Triprolidine: Hepatic metabolism via CYP450 enzymes. Pseudoephedrine: Partially metabolized in liver by N-demethylation; excreted unchanged in urine (70-90%). |
| Excretion | Renal: 80% (20% unchanged, 60% as metabolites). Fecal: 20% (unchanged and metabolites). Active tubular secretion of pseudoephedrine. |
| Half-life | Triprolidine: 3.2 hours; Pseudoephedrine: 5–8 hours (pH-dependent: alkaline urine prolongs). Terminal half-life for clinical use typically 4–6 hours. |
| Protein binding | Triprolidine: 60% bound to serum albumin; Pseudoephedrine: 20–30% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Triprolidine: 2.5–4.0 L/kg; Pseudoephedrine: 2.6–3.5 L/kg. Indicates extensive tissue distribution. |
| Bioavailability | Oral: Triprolidine 90–100%; Pseudoephedrine 100% (first-pass metabolism negligible). |
| Onset of Action | Oral: 30–60 minutes for antihistamine effect; 60–90 minutes for decongestant effect. |
| Duration of Action | Antihistamine: 4–6 hours; Decongestant: 4–6 hours. Extended-release formulations may last up to 12 hours. |
1 tablet (pseudoephedrine HCl 60 mg, triprolidine HCl 2.5 mg) orally every 4-6 hours; maximum 4 tablets in 24 hours.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | CrCl 30-50 mL/min: extend dosing interval to every 8 hours. CrCl 15-29 mL/min: every 12 hours. CrCl <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: consider extending interval to every 8 hours. Child-Pugh C: avoid use. |
| Pediatric use | Children 6-12 years: 1/2 tablet (pseudoephedrine 30 mg, triprolidine 1.25 mg) orally every 6 hours; max 2 tablets/24 hours. Children <6 years: not recommended. |
| Geriatric use | Start with 1/2 tablet (pseudoephedrine 30 mg, triprolidine 1.25 mg) orally every 8 hours; monitor for CNS excitation and anticholinergic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACTIFED (ACTIFED).
| Breastfeeding | Pseudoephedrine is excreted into breast milk; M/P ratio approximately 3.5. Triprolidine is present in milk. Potential for irritability, sleep disturbance in infants; may reduce milk supply. Use with caution; alternative preferred. Discontinue breastfeeding or drug based on necessity. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited human data; animal studies show fetal toxicity at high doses. Avoid unless benefit outweighs risk. Second/third trimesters: Risk of premature labor, neonatal respiratory depression, and withdrawal symptoms with prolonged use. Use lowest effective dose for shortest duration. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to triprolidine, pseudoephedrine, or any component","Severe hypertension or coronary artery disease","Monoamine oxidase inhibitor (MAOI) therapy (concurrent or within 14 days)","Narrow-angle glaucoma","Urinary retention","During or within 14 days of MAOI use"]
| Precautions | ["Cardiovascular effects: hypertension, palpitations, tachycardia, arrhythmias","CNS stimulation: nervousness, dizziness, insomnia, especially in elderly","May cause urinary retention in patients with prostatic hypertrophy","Use caution in patients with diabetes, hyperthyroidism, ischemic heart disease, increased intraocular pressure","Anticholinergic effects: dry mouth, blurred vision, constipation"] |
| Food/Dietary | Avoid high-tyramine foods (aged cheese, cured meats, fermented products) as pseudoephedrine may potentiate vasopressor effects. Grapefruit juice may decrease pseudoephedrine absorption; separate administration by at least 4 hours. |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate; assess for preterm labor symptoms, uterine hyperactivity. Fetal heart rate monitoring if used near term; observe neonate for withdrawal signs if used chronically. |
| Fertility Effects | No established effect on human fertility. Animal studies show no impairment at standard doses. Theoretical risk of vasoconstriction affecting ovarian blood flow, but clinical significance unknown. |
| Clinical Pearls | Actifed (pseudoephedrine + triprolidine) is contraindicated in patients with severe hypertension, coronary artery disease, or narrow-angle glaucoma. Pseudoephedrine can cause CNS stimulation and insomnia, so avoid evening dosing. Triprolidine is a first-generation antihistamine with significant anticholinergic effects; use caution in elderly or those with BPH, urinary retention, or asthma. |
| Patient Advice | Do not take with other cold or allergy medications containing decongestants or antihistamines. · Avoid alcohol and sedatives as they may increase drowsiness. · Do not crush or chew extended-release tablets; swallow whole. · Monitor for increased blood pressure or heart rate; discontinue if palpitations occur. · May cause dizziness; avoid driving or operating heavy machinery until you know how it affects you. |