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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TUXARIN ER (TUXARIN ER).
| Breastfeeding | Chlorpheniramine is excreted into breast milk in small amounts (M/P ratio not established). Pseudoephedrine is excreted into breast milk; M/P ratio approximately 3. Initial data indicate pseudoephedrine may reduce milk production by up to 24% with single doses. Use with caution; avoid in cases of established lactation insufficiency. American Academy of Pediatrics considers both drugs compatible with breastfeeding but may cause irritability in infants. |
| 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. |
■ 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 MAOIs; seizure disorder; history of anorexia nervosa or bulimia; abrupt discontinuation of alcohol, benzodiazepines, or anticonvulsants; known hypersensitivity to any component; use of other bupropion-containing products; concomitant use with linezolid or methylene blue.
| 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. |
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| 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. |