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. |
| Molecular Weight | 392.96 |
| Action Class | Sympathomimetic and Antihistamine |
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 | Avoid in first trimester unless clearly needed; potential risk of vascular disruption and gastroschisis associated with decongestants. |
| 2nd trimester | Use with caution; may cause uterine vasoconstriction and reduced placental perfusion. |
| 3rd trimester | Avoid in third trimester due to risk of uterine artery vasoconstriction and potential for neonatal respiratory depression or irritability from anticholinergic effects. |
Clinical note
MAOIs can cause hypertensive crisis Can cause insomnia and tachycardia.
| FDA category | Animal |
| Placental transfer | Both components cross the placenta. Pseudoephedrine readily crosses; chlorpheniramine is also transferred with measurable fetal concentrations. |
| Breastfeeding |
■ 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 | Hypertension, Tachycardia, Arrhythmias, Myocardial infarction, Stroke, Seizures, Psychosis, Urinary retention, Angle-closure glaucoma |
Severe hypertensionCoronary artery diseaseConcurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 daysAngle-closure glaucomaUrinary retentionSevere hepatic or renal impairmentHypersensitivity to any component
| 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. |
| Food/Dietary |
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| Pseudoephedrine and chlorpheniramine are excreted into breast milk. Pseudoephedrine may reduce milk production. Monitor infant for irritability, drowsiness, or antihistamine effects. Use lowest effective dose for shortest duration. |
| Lactation Rating | L3 - Moderately Safe |
| 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. |
| 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. |
| Avoid caffeine (coffee, tea, cola, chocolate) as it may increase stimulant effects of pseudoephedrine. Avoid alcohol as it potentiates sedative effects of chlorpheniramine. Grapefruit juice may affect metabolism of chlorpheniramine; limit intake. |
| Clinical Pearls | Pseudoephedrine is a sympathomimetic amine that can cause hypertension, tachycardia, and arrhythmias; avoid in severe hypertension, coronary artery disease, and hyperthyroidism. Chlorpheniramine is a sedating first-generation antihistamine with anticholinergic effects; caution in glaucoma, urinary retention, and elderly patients. Combination product may cause CNS stimulation or depression; monitor for insomnia with daytime use. |
| Patient Advice | Do not crush or chew extended-release tablets; swallow whole with a full glass of water. · Avoid taking within 4 hours of bedtime to prevent insomnia. · Do not use with other cold, allergy, or sleep medications containing antihistamines or decongestants. · May cause drowsiness or dizziness; avoid driving or operating machinery until effects are known. · Avoid alcohol and sedatives as they increase CNS depression. · Not recommended for children under 6 years, or use only under medical supervision. · Stop use and consult doctor if symptoms persist for more than 7 days or accompanied by fever. · Use with caution if you have high blood pressure, heart disease, diabetes, thyroid disease, or enlarged prostate. |