HYDROCODONE POLISTIREX AND CHLORPHENIRAMNE POLISTIREX
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Hydrocodone is a mu-opioid receptor agonist; chlorpheniramine is a histamine H1 receptor antagonist.
| Metabolism | Hydrocodone: CYP3A4 and CYP2D6 (to hydromorphone); chlorpheniramine: CYP2D6 and CYP3A4. |
| Excretion | Renal excretion: hydrocodone primarily as conjugates and unchanged drug (~60%), chlorpheniramine primarily as metabolites (~80% renal). Fecal excretion: minimal (<10%). |
| Half-life | Hydrocodone: 3.8-6 hours (extended-release formulation may have biphasic elimination). Chlorpheniramine: 21-27 hours. Clinical context: Steady-state reached in 2-5 days for chlorpheniramine. |
| Protein binding | Hydrocodone: 20-30% bound to albumin. Chlorpheniramine: 72-74% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Hydrocodone: 3.3-4.7 L/kg (extensive tissue distribution). Chlorpheniramine: 5-7 L/kg (large Vd due to high lipophilicity). |
| Bioavailability | Hydrocodone: 50-70% (oral, with first-pass metabolism). Chlorpheniramine: 25-50% (oral, extensive first-pass metabolism). |
| Onset of Action | Hydrocodone: 30-60 min (oral extended-release). Chlorpheniramine: 1-2 hours (oral). |
| Duration of Action | Hydrocodone: 12 hours (extended-release). Chlorpheniramine: 12-24 hours (polistirex formulation). |
| Molecular Weight | Hydrocodone: 299.37 Da; Chlorpheniramine: 274.79 Da. (Combination product: not applicable for single value) |
5 mL (hydrocodone 10 mg/chlorpheniramine 8 mg) orally every 12 hours; maximum 10 mL (20 mg hydrocodone/16 mg chlorpheniramine) per 24 hours.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | CrCl 30-50 mL/min: same dose but monitor for adverse effects. CrCl 10-29 mL/min: reduce dose by 50% or extend interval to every 18-24 hours. CrCl <10 mL/min: avoid use. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% or extend interval to every 18-24 hours. Child-Pugh Class C: avoid use. |
| Pediatric use | Not recommended for children under 18 years due to risk of respiratory depression and death. |
| Geriatric use | Start at lower end of dosing range (e.g., 2.5 mL every 12 hours). Monitor for respiratory depression, sedation, and constipation. Avoid in patients with significant respiratory compromise. |
| 1st trimester | Hydrocodone: Data limited; avoid if possible due to risk of congenital malformations (case-control studies suggest small increased risk of cardiac defects). Chlorpheniramine: Generally considered safe; preferred antihistamine in pregnancy. |
| 2nd trimester | Hydrocodone: Use lowest effective dose for shortest duration; risk of fetal dependence and withdrawal. Chlorpheniramine: Safe. |
| 3rd trimester | Hydrocodone: Avoid prolonged use or high doses near term due to risk of neonatal opioid withdrawal syndrome and respiratory depression. Chlorpheniramine: Safe. |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Placental transfer | Both hydrocodone and chlorpheniramine cross the placenta. Hydrocodone: readily transferred; detectable in fetal blood. Chlorpheniramine: crosses placenta but limited data. |
■ FDA Black Box Warning
Risk of opioid addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; risks from concomitant use with benzodiazepines or other CNS depressants; neonatal opioid withdrawal syndrome; and risks of medication errors involving hydrocodone.
| Common Effects | Cough |
| Serious Effects |
Hypersensitivity to hydrocodone, chlorpheniramine, or any componentSignificant respiratory depressionAcute or severe bronchial asthma in unmonitored settingParalytic ileusConcurrent use of MAO inhibitors or within 14 daysKnown CYP2D6 ultra-rapid metabolizer (risk of hydrocodone toxicity)
| Precautions | Addiction, abuse, and misuse, Life-threatening respiratory depression, Accidental ingestion, Neonatal opioid withdrawal syndrome, Risks from concomitant use with CNS depressants, Risks of medication errors, Interaction with MAOIs, Adrenal insufficiency, Hypotension and bradycardia, Seizures, Opioid-induced hyperalgesia, Severe hypotension, Gastrointestinal effects, Anticholinergic effects (chlorpheniramine) |
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| Breastfeeding | Hydrocodone: Enters breast milk; use caution in nursing mothers, especially if ultra-rapid metabolizer (CYP2D6) due to risk of infant opioid toxicity. Chlorpheniramine: Excreted in milk; use caution as antihistamines may cause drowsiness or irritability in infants. Best to use non-sedating alternatives. |
| Lactation Rating | L3 (Moderately Safe) - Hydrocodone: L3; Chlorpheniramine: L2 but combination rated L3 due to hydrocodone. |
| Teratogenic Risk | First trimester: Limited data; potential for neural tube defects (OR 1.3 for opioids). Second/third trimester: Risk of neonatal opioid withdrawal syndrome (NOWS); use only if benefit outweighs risk. Avoid near term due to respiratory depression in neonate. |
| Fetal Monitoring | Maternal: Respiratory rate, sedation level, bowel function, signs of abuse/dependence. Fetal: Ultrasound for growth restriction if chronic use; non-stress test or biophysical profile if opioid dependence. Neonatal: Observe for NOWS (irritability, poor feeding, tremors) for 3-5 days post-delivery. |
| Fertility Effects | Opioids may disrupt menstrual cycle via hypothalamic-pituitary-gonadal axis suppression (decreased LH/FSH), potentially impairing ovulation. Reversible upon discontinuation. No direct evidence of impaired fertility in males or females. |
| Food/Dietary | Avoid alcohol and grapefruit juice (grapefruit juice may increase hydrocodone levels). No specific food restrictions; take with or without food. If gastrointestinal upset, take with food or milk. |
| Clinical Pearls | Hydrocodone polistirex is an extended-release opioid agonist; chlorpheniramine polistirex is an extended-release antihistamine. This combination is used for cough and upper respiratory symptoms. The polistirex complex provides sustained release; do not crush or chew capsules (releases immediate high dose of hydrocodone, risk of fatal overdose). Each 5 mL suspension contains hydrocodone polistirex equivalent to 10 mg hydrocodone bitartrate and chlorpheniramine polistirex equivalent to 8 mg chlorpheniramine maleate (Tussionex Penkinetic). Avoid use with other CNS depressants, MAOIs within 14 days. Respiratory depression risk; monitor for sedation, constipation. Use lowest effective dose for shortest duration. Not indicated for pediatric patients <6 years. Capsule strength (not currently marketed) may vary; check product labeling. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting doctor. · Do not crush, chew, dissolve, or break capsules (may cause dangerous overdose). Swallow whole. · Shake suspension well before each use. Use only the dosing device provided. · Avoid alcohol and other sedatives (benzodiazepines, sleep aids, muscle relaxants) unless approved by your doctor. · This drug can cause drowsiness or dizziness. Do not drive or operate machinery until you know how it affects you. · Common side effects: constipation, nausea, dry mouth, dizziness. Report severe drowsiness, confusion, shallow breathing, or difficulty passing urine. · Store at room temperature away from heat and moisture. Dispose of unused medication via drug take-back program or flushing (FDA recommendation for opioids to prevent accidental overdose). · Do not share with others; may cause severe harm or death · If you miss a dose, skip it and take next at regular time. Do not double. · Inform doctor if pregnant, planning pregnancy, or breastfeeding. |