PSEUDOEPHEDRINE HYDROCHLORIDE AND CHLORPHENIRAMINE MALEATE
Clinical safety rating: safe
MAOIs can cause hypertensive crisis Can cause insomnia and tachycardia.
Pseudoephedrine is a sympathomimetic amine that acts as a vasoconstrictor via alpha-1 adrenergic receptor activation, reducing nasal congestion. Chlorpheniramine is a first-generation antihistamine that competitively inhibits histamine H1 receptors, suppressing allergic symptoms.
| Metabolism | Pseudoephedrine: partially hepatic metabolism (N-demethylation) to inactive metabolites; also renal excretion of unchanged drug. Chlorpheniramine: extensively metabolized in liver via CYP2D6 and other CYP enzymes to desmethylchlorpheniramine and other metabolites. |
| Excretion | Pseudoephedrine: renal excretion of unchanged drug (70-90%) with pH-dependent elimination (acidic urine increases excretion). Chlorpheniramine: renal excretion of metabolites (65-75%) and unchanged drug (15-20%); biliary/fecal elimination accounts for approximately 20%. |
| Half-life | Pseudoephedrine: 5-8 hours (normal renal function); prolonged to 12-24 hours in renal impairment. Chlorpheniramine: 12-24 hours (range 10-36 hours); extended in hepatic impairment. |
| Protein binding | Pseudoephedrine: <20% bound to albumin. Chlorpheniramine: 70-75% bound to albumin. |
| Volume of Distribution | Pseudoephedrine: 2.6-3.3 L/kg (wide distribution). Chlorpheniramine: 3-5 L/kg (extensive tissue distribution). |
| Bioavailability | Pseudoephedrine: oral bioavailability 100% (almost complete absorption). Chlorpheniramine: oral bioavailability approximately 40-50% due to first-pass metabolism. |
| Onset of Action | Pseudoephedrine: oral ~30-60 minutes. Chlorpheniramine: oral ~1-3 hours. |
| Duration of Action | Pseudoephedrine: 4-6 hours (immediate-release); sustained-release up to 12-24 hours. Chlorpheniramine: 4-6 hours (single dose); up to 12-24 hours with extended-release formulations. |
1 tablet orally every 4-6 hours not to exceed 4 tablets in 24 hours; each tablet contains pseudoephedrine HCl 60 mg and chlorpheniramine maleate 4 mg.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | CrCl 30-50 mL/min: administer every 6-8 hours; CrCl 10-29 mL/min: administer every 8-12 hours; CrCl <10 mL/min: use not recommended. |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50% or extend interval; Child-Pugh class C: use is contraindicated. |
| Pediatric use | Children 6-11 years: 1/2 tablet (pseudoephedrine 30 mg/chlorpheniramine 2 mg) every 4-6 hours, max 2 tablets in 24 hours; children 12 years and older: same as adult. |
| Geriatric use | Initiate at half the adult dose; monitor for anticholinergic effects, dizziness, and hypertension; maximum duration 5 days. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause hypertensive crisis Can cause insomnia and tachycardia.
| FDA category | Animal |
| Breastfeeding | Pseudoephedrine: small amounts excreted (M/P ratio ~2.8) which may cause infant irritability; may reduce milk production (decrease prolactin). Chlorpheniramine: limited data; excreted in small amounts; antihistamines may cause drowsiness. Caution advised; monitor infant for sedation or irritability. |
| Teratogenic Risk | First trimester: Pseudoephedrine is a sympathomimetic associated with a possible increased risk of gastroschisis; chlorpheniramine is generally considered low risk with some studies suggesting no increased risk of major malformations. Second/third trimester: Pseudoephedrine may reduce uteroplacental blood flow; avoid near term due to risk of neonatal tachycardia, irritability. Overall, use only if clearly needed. |
■ FDA Black Box Warning
This combination product does not have an FDA boxed warning; however, caution is advised regarding cardiovascular effects due to pseudoephedrine.
| Common Effects | Insomnia |
| Serious Effects |
Severe hypertension, coronary artery disease, narrow-angle glaucoma, urinary retention, peptic ulcer, concurrent or recent (within 14 days) MAOI therapy, hypersensitivity to any component, children < 6 years (for some formulations), severe renal impairment.
| Precautions | Cardiovascular disease (hypertension, ischemic heart disease, arrhythmias), hyperthyroidism, diabetes, glaucoma, prostatic hyperplasia, urinary retention, pregnancy (Category C), elderly patients, breastfeeding, concurrent use of MAOIs or within 14 days, severe liver disease. |
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| Fetal Monitoring | Maternal: blood pressure monitoring (risk of hypertension with pseudoephedrine); fetal: heart rate monitoring if used near term. Assess infant for CNS stimulation/sedation if used during breastfeeding. |
| Fertility Effects | No specific human studies. Pseudoephedrine may affect sperm motility in vitro; chlorpheniramine has no known effect. Both drugs are not expected to impair fertility significantly at standard doses. |