CORSYM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CORSYM (CORSYM).
Phenylephrine is a selective α1-adrenergic receptor agonist causing vasoconstriction; chlorpheniramine is a first-generation antihistamine that competitively inhibits histamine at H1 receptors.
| Metabolism | Phenylephrine: primarily via monoamine oxidase (MAO) and sulfotransferase; chlorpheniramine: extensively metabolized by CYP2D6 and other CYP enzymes. |
| Excretion | CORSYM (hydrocodone polistirex and chlorpheniramine polistirex) is an extended-release formulation. Hydrocodone is metabolized primarily in the liver via CYP3A4 and CYP2D6 to norhydrocodone, hydromorphone, and other metabolites. Excretion is predominantly renal (about 90%) as unchanged drug and metabolites, with approximately 10% excreted in feces via biliary elimination. Chlorpheniramine is metabolized in the liver and excreted renally as metabolites (about 70-80%) and unchanged drug (about 10-20%), with minor fecal excretion. |
| Half-life | The terminal elimination half-life for hydrocodone from the CORSYM formulation is approximately 8-10 hours, reflecting the extended-release profile. This allows for twice-daily dosing. Hydrocodone's half-life in immediate-release forms is about 3-4 hours, so the polistirex complex prolongs absorption. Chlorpheniramine has a half-life of about 20-24 hours in adults, but in the polistirex formulation, its half-life is extended to approximately 18-22 hours, supporting once-daily dosing for the antihistamine component. |
| Protein binding | Hydrocodone is approximately 19-30% bound to plasma proteins, primarily albumin. Chlorpheniramine is about 70-72% bound to plasma proteins, mainly albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Hydrocodone has a volume of distribution (Vd) of about 3.3-4.4 L/kg, indicating extensive tissue distribution. Chlorpheniramine has a Vd of approximately 3-6 L/kg, also suggesting widespread distribution. The large Vd reflects significant sequestration in tissues, including the central nervous system. |
| Bioavailability | The oral bioavailability of hydrocodone from CORSYM is about 70-80% after accounting for first-pass metabolism. Chlorpheniramine has an oral bioavailability of about 25-50% due to extensive first-pass metabolism. The polistirex complex does not significantly alter the extent of absorption but controls the rate. |
| Onset of Action | Following oral administration, the onset of antitussive action for hydrocodone is observed within 20-30 minutes. The antihistamine effect (chlorpheniramine) may begin within 30-60 minutes. However, due to the extended-release nature, peak effects are delayed; full clinical efficacy may take 1-2 hours. |
| Duration of Action | The duration of antitussive action of hydrocodone from CORSYM is approximately 12-14 hours, allowing for twice-daily dosing. Chlorpheniramine's antihistamine effect lasts about 12-24 hours, supporting once-daily administration. However, the product is typically dosed every 12 hours for both components, providing sustained symptom relief. |
Adults: 100 mg orally once daily, taken with water at least 1 hour before meals. Maximum dose 100 mg/day.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | Not recommended for use in patients with CrCl < 30 mL/min. No dose adjustment required for CrCl ≥ 30 mL/min. |
| Liver impairment | Contraindicated in patients with Child-Pugh class B or C hepatic impairment. Use with caution in Child-Pugh class A; consider starting at 50 mg once daily. |
| Pediatric use | Not approved for pediatric use. Safety and efficacy in patients < 18 years have not been established. |
| Geriatric use | No specific dose adjustment recommended; consider lower starting dose (50 mg once daily) due to potential age-related renal dysfunction and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CORSYM (CORSYM).
| Breastfeeding | Chlorpheniramine: small amounts excreted in breast milk; possible irritability, drowsiness, or apnea in infant. Phenylephrine: unknown excretion but minimal oral bioavailability; M/P ratio not established. Use with caution; consider alternative decongestants with better safety profiles (e.g., pseudoephedrine with monitoring). |
| Teratogenic Risk | CORSYM (chlorpheniramine/phenylephrine) is FDA pregnancy category B. No evidence of teratogenicity in animal studies; inadequate human studies. First trimester: risk cannot be excluded; use only if clearly needed. Second/third trimesters: avoid near term due to potential for paradoxical neonatal CNS stimulation or withdrawal symptoms from chlorpheniramine, and possible association with maternal hypertension and reduced uterine blood flow from phenylephrine. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to any component","severe hypertension","severe coronary artery disease","MAOI use within 14 days"]
| Precautions | ["Hypertension","cardiovascular disease","hyperthyroidism","diabetes mellitus","prostatic hypertrophy","glaucoma","MAOI use within 14 days","pregnancy and lactation"] |
| Food/Dietary | Avoid alcohol-containing foods or beverages. Grapefruit juice may increase absorption; avoid concurrent use. High-fat meals may affect drug release; maintain consistent dietary patterns. |
| Clinical Pearls |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of CNS stimulation. Fetal monitoring: ultrasound for growth restriction if prolonged use; fetal heart rate monitoring if maternal hypertension occurs. Observe neonate for irritability, sedation, or respiratory depression after delivery if used near term. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment of fertility with chlorpheniramine; phenylephrine may cause vasoconstriction affecting uterine perfusion but no direct fertility impact. |
| CORSYM (hydrocodone polistirex and chlorpheniramine polistirex) is an extended-release antitussive/antihistamine. Monitor for CNS depression and respiratory depression, especially in patients on other CNS depressants. The polistirex formulation provides prolonged release; do not crush or chew. Not recommended for children under 18 years due to risk of respiratory depression. Use with caution in patients with asthma, COPD, or increased intracranial pressure. Abuse potential exists; prescribe smallest quantity for shortest duration. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency. · Swallow capsules whole; do not crush, chew, or dissolve. · Avoid alcohol and other sedatives (e.g., benzodiazepines, opioids) due to risk of severe drowsiness or breathing problems. · Do not drive or operate machinery until you know how CORSYM affects you; may cause drowsiness or dizziness. · Store at room temperature away from moisture and heat; keep out of reach of children. · Do not stop suddenly; consult doctor for discontinuation plan to avoid withdrawal symptoms. |