GUAIFENESIN AND PSEUDOEPHEDRINE HYDROCHLORIDE
Clinical safety rating: safe
MAOIs can cause hypertensive crisis Can cause insomnia and tachycardia.
Guaifenesin is an expectorant that increases respiratory tract fluid secretions, reducing mucus viscosity. Pseudoephedrine hydrochloride is a sympathomimetic amine that directly stimulates alpha-adrenergic receptors in the respiratory tract mucosa, causing vasoconstriction and nasal decongestion. It also has weak beta-adrenergic activity.
| Metabolism | Guaifenesin is metabolized via oxidation to beta-(2-methoxyphenoxy)lactic acid. Pseudoephedrine is partially metabolized by hepatic N-demethylation to an inactive metabolite (norpseudoephedrine) and undergoes renal excretion as unchanged drug. |
| Excretion | Guaifenesin: Renal, approximately 60% unchanged and 40% as metabolites. Pseudoephedrine: Renal, 55-75% unchanged, dose-dependent with acidic urine enhancing elimination. |
| Half-life | Guaifenesin: 1 hour (short half-life requiring frequent dosing). Pseudoephedrine: 4-6 hours (prolonged to 16-20 hours with alkaline urine). |
| Protein binding | Guaifenesin: Approximately 0% (negligible). Pseudoephedrine: Approximately 20% bound to plasma proteins. |
| Volume of Distribution | Guaifenesin: 1-2 L/kg (widely distributed). Pseudoephedrine: 2-3 L/kg (extensive tissue distribution). |
| Bioavailability | Oral: Guaifenesin: approximately 40-50% (first-pass metabolism). Pseudoephedrine: approximately 90% (well absorbed, minimal first-pass). |
| Onset of Action | Oral: Guaifenesin: 30 minutes; Pseudoephedrine: 30 minutes for decongestant effect. |
| Duration of Action | Guaifenesin: 4-6 hours; Pseudoephedrine: 4-6 hours (extended-release formulations up to 12 hours). |
| Molecular Weight | Guaifenesin 198.22 Da; Pseudoephedrine HCl 201.69 Da; combination product average ~200 Da. |
Guaifenesin 400 mg and pseudoephedrine hydrochloride 60 mg orally every 4 to 6 hours as needed, not to exceed 4 doses per 24 hours.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | CrCl 30-50 mL/min: administer every 6 hours; CrCl <30 mL/min: not recommended due to pseudoephedrine accumulation. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment (Child-Pugh C) as pseudoephedrine metabolism may be reduced. |
| Pediatric use | Children 6-12 years: guaifenesin 200 mg and pseudoephedrine 30 mg orally every 4-6 hours, max 4 doses/24h; children >12 years: adult dose. Not recommended under 6 years. |
| Geriatric use | Start with lower doses (e.g., half the adult dose) due to increased sensitivity to pseudoephedrine and higher risk of adverse effects; maximum 4 doses per 24 hours. |
| 1st trimester | Limited human data; animal studies not available. Generally avoid unless benefit outweighs risk. Consider alternative therapies first trimester. |
| 2nd trimester | Use only if clearly needed; no known teratogenicity. Monitor for maternal hypertension and fetal heart rate. |
| 3rd trimester | Avoid near term due to risk of uterine atony, premature closure of ductus arteriosus (pseudoephedrine), and potential for neonatal irritability. |
Clinical note
MAOIs can cause hypertensive crisis Can cause insomnia and tachycardia.
| FDA category | Animal |
| Placental transfer | Both components cross the placenta. Pseudoephedrine is known to cross, data for guaifenesin limited but likely. |
| Breastfeeding |
■ FDA Black Box Warning
None
| Common Effects | Insomnia |
| Serious Effects |
Severe coronary artery diseaseUncontrolled hypertensionNarrow-angle glaucomaUrinary retentionConcurrent MAO inhibitor therapy (or within 14 days)Hypersensitivity to any component
| Precautions | Do not exceed recommended dosage; may cause nervousness, dizziness, or sleeplessness. Use caution in patients with hypertension, cardiovascular disease, diabetes, hyperthyroidism, increased intraocular pressure, prostatic hypertrophy, or during pregnancy/lactation. Avoid use with MAO inhibitors or within 14 days of stopping such therapy. |
| Food/Dietary | Avoid caffeine-containing foods and beverages (e.g., coffee, tea, chocolate) as they may increase CNS stimulation. No other significant food interactions. |
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| Guaifenesin is excreted into breast milk in low amounts; pseudoephedrine is excreted in higher concentrations (possibly up to 4% of maternal dose) and may cause irritability or decreased milk production. Use with caution, monitor infant for agitation. |
| Lactation Rating | L3 (Moderately Safe) - Limited data; potential for adverse effects in infant. |
| Teratogenic Risk | First trimester: Inadequate human data; guaifenesin has been associated with neural tube defects in some retrospective studies, but no consistent pattern established. Pseudosphedrine may cause vasoconstriction; theoretical risk of uteroplacental insufficiency. Second trimester: Limited data; no major teratogenic signals. Third trimester: Pseudosphedrine may reduce uterine blood flow; avoid near term due to risk of uterine artery vasoconstriction. Overall, avoid in first trimester; use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate, especially in preeclampsia or hypertension. Fetal heart rate monitoring if used near term. Assess for signs of uterine tachysystole or fetal distress. No specific drug level monitoring required. |
| Fertility Effects | No known adverse effects on fertility. Pseudosphedrine may theoretically affect fallopian tube motility via adrenergic effects, no clinical data. Guaifenesin not associated with fertility impairment. |
| Clinical Pearls | Guaifenesin is an expectorant that increases respiratory tract fluid secretion to reduce mucus viscosity; pseudoephedrine is a sympathomimetic decongestant causing vasoconstriction. Avoid in patients with uncontrolled hypertension, severe coronary artery disease, or concurrent MAOI use. Monitor for CNS stimulation, tachycardia, and urinary retention. Guaifenesin can interfere with urine 5-HIAA and VMA tests. |
| Patient Advice | Do not crush or chew extended-release tablets; swallow whole. · Avoid taking within 4 hours of bedtime to prevent insomnia. · Drink plenty of fluids to help loosen mucus. · Do not use if you have high blood pressure, heart disease, or are taking MAOIs. · Stop use and consult a doctor if symptoms persist or worsen after 7 days, or if fever develops. |