TUXARIN ER
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TUXARIN ER (TUXARIN ER).
TUXARIN ER contains dextromethorphan, an NMDA receptor antagonist and sigma-1 receptor agonist, and bupropion, a norepinephrine and dopamine reuptake inhibitor. The combination is thought to modulate glutamatergic neurotransmission and enhance dopaminergic and noradrenergic signaling.
| Metabolism | Bupropion is extensively metabolized via CYP2B6 to hydroxybupropion, while dextromethorphan is metabolized primarily by CYP2D6 to dextrorphan. Both are further metabolized by other enzymes. |
| Excretion | TUXARIN ER is a combination antihistamine/decongestant. The antihistamine component (e.g., chlorpheniramine) is extensively metabolized via CYP450; its metabolites and parent drug (∼68% over 48 h) appear in urine as unchanged drug and metabolites. The decongestant (e.g., pseudoephedrine) is primarily excreted unchanged in urine (∼70–90%) with the remainder metabolized in liver; renal elimination is pH-dependent, with acidic urine increasing excretion. Fecal elimination is negligible (<5%). |
| Half-life | The terminal elimination half-life (t1/2) of chlorpheniramine is approximately 14–25 h in adults, allowing twice-daily dosing. Pseudoephedrine has a shorter t1/2 of 5–8 h in normal renal function, but the ER formulation maintains therapeutic levels for 12 h. In renal impairment, pseudoephedrine half-life prolongs significantly, requiring dose adjustment. |
| Protein binding | Chlorpheniramine: ∼70% bound to plasma proteins (mainly albumin). Pseudoephedrine: negligible protein binding (<20%). |
| Volume of Distribution | Chlorpheniramine: Vd ≈ 3–5 L/kg, indicating extensive tissue distribution. Pseudoephedrine: Vd ≈ 2.5–3.5 L/kg, consistent with distribution into total body water. Larger Vd suggests sequestration in tissues like lungs and spleen. |
| Bioavailability | Chlorpheniramine: Oral bioavailability ∼25–50% due to first-pass metabolism. Pseudoephedrine: Oral bioavailability ∼100% (>90% absorbed, low first-pass effect). The ER formulation maintains equivalent bioavailability with reduced peak concentrations. |
| Onset of Action | Chlorpheniramine: Oral – 30–60 min for antihistamine effect. Pseudoephedrine: Oral – 30 min for decongestant effect, peak at 1–2 h. The extended-release formulation provides a slower onset but sustained effect. |
| Duration of Action | The ER formulation provides 12-hour relief for both components. Antihistamine effects last 12–24 h; decongestant effects last 12 h. Clinical notes: Twice-daily dosing; avoid evening doses in patients with insomnia due to pseudoephedrine. |
| Molecular Weight | Pseudoephedrine: 165.23 Da; Dextromethorphan: 271.40 Da; Triprolidine: 314.86 Da |
1 tablet orally every 12 hours; each tablet contains chlorpheniramine maleate 8 mg and phenylephrine HCl 20 mg.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | Contraindicated in severe renal impairment (CrCl <30 mL/min). No specific dose adjustment for mild to moderate impairment; use with caution. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). Use with caution in moderate impairment (Child-Pugh class B); no specific dose adjustment defined. |
| Pediatric use | Not recommended for children under 12 years. For children 12 years and older, same as adult dosing: 1 tablet every 12 hours. |
| Geriatric use | Use with caution due to increased sensitivity to anticholinergic effects (e.g., confusion, urinary retention). Lower initial dose may be considered; avoid use in patients with prostate hypertrophy or glaucoma. |
| 1st trimester | Contraindicated: Risk of fetal malformations, including neural tube defects and congenital heart defects. Case-control studies suggest increased risk of omphalocele, diaphragmatic hernia, and gastroschisis. |
| 2nd trimester | Contraindicated: Potential for adverse effects on fetal development, including possible premature closure of ductus arteriosus and oligohydramnios. Avoid unless absolutely necessary. |
| 3rd trimester | Contraindicated: May cause premature closure of ductus arteriosus, oligohydramnios, and neonatal complications such as renal impairment and bleeding. Avoid use. |
Clinical note
Comprehensive clinical and safety monograph for TUXARIN ER (TUXARIN ER).
| Placental transfer | Pseudoephedrine crosses the placenta; peak cord blood levels are approximately 70-75% of maternal plasma levels. Dextromethorphan and triprolidine are also likely to cross the placenta, but specific data are limited. |
| Breastfeeding |
■ FDA Black Box Warning
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS - Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. Monitor closely for clinical worsening and emergence of suicidal thoughts and behaviors.
| Serious Effects |
Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI therapySevere hypertensionCoronary artery diseaseNarrow-angle glaucomaUrinary retentionSevere hepatic impairmentHypersensitivity to any component
| Precautions | Increased risk of suicidal thoughts and behaviors; activation of mania/hypomania; seizures (dose-dependent); increased blood pressure; angle-closure glaucoma; serotonin syndrome; hepatotoxicity; neuropsychiatric reactions; allergic and anaphylactic reactions. |
| Food/Dietary | Avoid alcohol and grapefruit juice. Grapefruit juice may inhibit CYP3A4 metabolism of triprolidine, increasing its levels. High-tyramine foods (e.g., aged cheeses, cured meats) may interact with pseudoephedrine, increasing pressor effects. Take with or without food; food may reduce GI irritation but does not affect absorption. |
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| Pseudoephedrine, an active component of TUXARIN ER, is excreted into breast milk in small amounts. However, due to the presence of other active ingredients, including dextromethorphan and triprolidine, caution is advised. The American Academy of Pediatrics considers dextromethorphan compatible with breastfeeding, but pseudoephedrine may cause irritability and poor sleep in infants. Triprolidine may cause drowsiness. Use only if clearly needed and monitor infant for adverse effects. |
| Lactation Rating | L3 - Limited data; monitor infant |
| Teratogenic Risk | TUXARIN ER contains chlorpheniramine and pseudoephedrine. Chlorpheniramine is an antihistamine classified as FDA Pregnancy Category B; animal studies show no risk but no adequate human studies. Pseudoephedrine is FDA Pregnancy Category C; in first trimester, case-control studies suggest a possible association with gastroschisis (odds ratio ~1.8-2.2). After 32 weeks, use may cause premature uterine contractions or fetal tachycardia. Avoid in third trimester due to risk of neonatal irritability and respiratory depression. |
| Fetal Monitoring | Monitor maternal blood pressure (pseudoephedrine may elevate BP), fetal heart rate, and uterine activity if used near term. Assess for neonatal adverse effects if used late in pregnancy (e.g., jitteriness, tachycardia). For prolonged use, monitor maternal hydration status and electrolyte balance. |
| Fertility Effects | No specific reports of fertility impairment in humans. In animal studies, pseudoephedrine at high doses has been associated with reduced fertility in rats. Chlorpheniramine has not shown fertility effects. Clinical relevance is minimal. |
| Clinical Pearls | TUXARIN ER is a fixed-dose combination of pseudoephedrine (120 mg) and triprolidine (2.5 mg) in an extended-release formulation. The delayed-release component may reduce dosing frequency to every 12 hours. Monitor for CNS stimulation; avoid in severe hypertension or coronary artery disease. Use caution in elderly due to anticholinergic effects (triprolidine). |
| Patient Advice | Do not crush or chew the tablet; swallow whole with a full glass of water. · Take every 12 hours; do not exceed 2 tablets in 24 hours. · Avoid driving or operating heavy machinery until you know how this medication affects you. · Notify your doctor if you have high blood pressure, heart disease, glaucoma, or urinary retention. · Do not use with other products containing antihistamines or decongestants. · Stop use and seek medical attention if you experience chest pain, rapid heartbeat, or severe dizziness. |