TUSSIONEX PENNKINETIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TUSSIONEX PENNKINETIC (TUSSIONEX PENNKINETIC).
Tussionex Pennkinetic is a combination of hydrocodone, a mu-opioid receptor agonist, and chlorpheniramine, a histamine H1 receptor antagonist. Hydrocodone binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception; it also suppresses cough reflex by direct action on the cough center in the medulla. Chlorpheniramine competitively blocks H1 receptors, reducing symptoms of allergic rhinitis such as sneezing, rhinorrhea, and pruritus.
| Metabolism | Hydrocodone is metabolized primarily by CYP2D6 and CYP3A4 to hydromorphone (active) and other metabolites. Chlorpheniramine is metabolized by CYP2D6 and other pathways. |
| Excretion | Tussionex Pennkinetic (hydrocodone/chlorpheniramine) is primarily excreted renally. Hydrocodone and its metabolites (e.g., hydromorphone, norhydrocodone) are eliminated mainly in urine as conjugates, with approximately 60-70% of the dose recovered in urine over 72 hours, predominantly as glucuronide and sulfate conjugates. Biliary/fecal excretion accounts for about 10-20%, with the remainder via other routes. Chlorpheniramine is extensively metabolized in the liver and excreted renally as metabolites and unchanged drug (less than 1% unchanged). |
| Half-life | Hydrocodone: Terminal elimination half-life is approximately 3.8-4.5 hours in adults. With extended-release formulation (Pennkinetic), the half-life may be prolonged due to slow absorption, but the elimination half-life itself is not significantly altered. Chlorpheniramine: Terminal half-life is approximately 21-27 hours. Clinically, the prolonged half-life of chlorpheniramine contributes to sustained antihistamine effects. |
| Protein binding | Hydrocodone: approximately 30-40% bound to plasma proteins. Chlorpheniramine: approximately 70% bound to plasma proteins, mainly albumin and possibly other proteins. |
| Volume of Distribution | Hydrocodone: Vd is approximately 3-4 L/kg (range 3.0-4.7 L/kg), indicating extensive tissue distribution. Chlorpheniramine: Vd is approximately 3-5 L/kg, also indicating wide distribution. Large Vd suggests high tissue penetration. |
| Bioavailability | Oral bioavailability of hydrocodone is approximately 70-80% (first-pass metabolism). Chlorpheniramine is well absorbed orally with bioavailability of about 25-50% due to extensive first-pass metabolism. For Tussionex Pennkinetic, the extended-release formulation provides sustained absorption. |
| Onset of Action | Oral (extended-release suspension): Peak plasma concentrations are achieved in approximately 1-2 hours for hydrocodone and 3-5 hours for chlorpheniramine. The onset of antitussive effect is typically within 30-60 minutes. |
| Duration of Action | Extended-release formulation provides cough suppression for up to 12 hours per dose. The antihistamine effect of chlorpheniramine lasts longer, typically 12-24 hours. Clinical duration may vary with dosing interval (every 12 hours recommended). |
| Molecular Weight | 299.4 |
Oral: 10 mL (equivalent to 10 mg hydrocodone and 10 mg chlorpheniramine) every 12 hours; maximum 20 mL per day.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | GFR <30 mL/min: Not recommended due to accumulation of hydrocodone metabolites. |
| Liver impairment | Child-Pugh Class C: contraindicated; Class A or B: reduce dose by 50% or extend interval, monitor closely. |
| Pediatric use | Children ≥6 years: 2.5 mL every 12 hours; maximum 5 mL per day. Children <6 years: contraindicated. |
| Geriatric use | Initiate at lower dose (e.g., 2.5 mL every 12 hours) due to increased sensitivity and renal impairment risk; maximum 5 mL per day. |
| 1st trimester | Avoid: Contains hydrocodone and chlorpheniramine. Hydrocodone is an opioid with teratogenic potential, risk of congenital malformations. Chlorpheniramine may be associated with minor malformations. Benefits rarely outweigh risks in first trimester. |
| 2nd trimester | Use with caution: Hydrocodone may cause fetal dependence and withdrawal; chlorpheniramine has limited safety data. Prescribe only if clearly needed and for shortest duration. |
| 3rd trimester | Avoid: Prolonged use of hydrocodone can cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression. Chlorpheniramine may cause neonatal irritability. Contraindicated near term. |
Clinical note
Comprehensive clinical and safety monograph for TUSSIONEX PENNKINETIC (TUSSIONEX PENNKINETIC).
| Placental transfer | Hydrocodone and chlorpheniramine cross the placenta. Hydrocodone is a small molecule (molecular weight 299.4 Da) with high placental transfer. Chlorpheniramine (molecular weight 274.8 Da) also crosses, with concentrations in cord blood similar to maternal plasma. |
■ FDA Black Box Warning
WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and SEROTONIN SYNDROME. Tussionex Pennkinetic exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Serious, life-threatening, or fatal respiratory depression may occur. Accidental ingestion of even one dose, especially by children, can result in fatal overdose. Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome. Concomitant use with CYP3A4 inhibitors or discontinuation of CYP3A4 inducers may increase hydrocodone concentrations. Concomitant use with benzodiazepines or other CNS depressants may cause profound sedation, respiratory depression, coma, and death. Concomitant use with serotonergic drugs may cause serotonin syndrome.
| Serious Effects |
Hypersensitivity to hydrocodone, chlorpheniramine, or any componentSignificant respiratory depressionAcute or severe bronchial asthma in an unmonitored settingParalytic ileusConcurrent use of MAO inhibitors or within 14 daysPostoperative management in children after tonsillectomy/adenoidectomyChildren < 6 years of age
| Precautions | Addiction, abuse, and misuse, Life-threatening respiratory depression, Accidental ingestion (especially in children), Neonatal opioid withdrawal syndrome, CYP3A4 and CYP2D6 interactions, Risks from concomitant use with benzodiazepines or other CNS depressants, Serotonin syndrome, Severe hypotension, Gastrointestinal adverse effects (e.g., constipation), Seizures in patients with seizure disorders, Avoid use in patients with impaired consciousness or coma, Avoid use in patients with known or suspected gastrointestinal obstruction, Use caution in patients with head injury, increased intracranial pressure, or impaired renal/hepatic function |
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| Breastfeeding |
| Hydrocodone and chlorpheniramine are excreted into breast milk. Hydrocodone may cause infant sedation, respiratory depression, and withdrawal. Chlorpheniramine may decrease milk production and cause infant drowsiness. Use is not recommended; consider non-opioid alternatives. Monitor infant for signs of CNS depression. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | First trimester: Data insufficient in humans; animal studies show no teratogenicity at therapeutic doses. Second and third trimesters: Hydrocodone may cause neonatal opioid withdrawal syndrome (NOWS) with prolonged use. Chlorpheniramine is generally considered low risk; no major malformations reported. |
| Fetal Monitoring | Assess fetal growth and amniotic fluid index with prolonged use due to potential opioid effects. Monitor for signs of neonatal opioid withdrawal if used near term. Assess maternal respiratory status and sedation level. Urine drug screening recommended if abuse suspected. |
| Fertility Effects | No known direct effects on fertility. Opioid use may disrupt menstrual cycle and reduce libido; chlorpheniramine has no known adverse fertility effects. |
| Food/Dietary | Avoid grapefruit juice due to potential for increased hydrocodone absorption and toxicity. High-fat meals may delay absorption but not affect overall exposure. Avoid alcohol as it potentiates CNS depression and can increase the release rate of hydrocodone from the polistirex matrix. |
| Clinical Pearls | TUSSIONEX PENNKINETIC (hydrocodone polistirex/chlorpheniramine polistirex) is an extended-release suspension. The polistirex matrix provides sustained release over 12 hours; do not crush or chew. Avoid use in children under 6 years due to risk of respiratory depression. Contains hydrocodone, a Schedule II controlled substance with abuse potential. May cause QTc prolongation; avoid in patients with electrolyte abnormalities or on other QTc-prolonging drugs. |
| Patient Advice | Shake the bottle well before each use. · Measure dose with the provided dosing cup; do not use household spoons. · Do not crush, chew, or dissolve the medication; it must be swallowed whole. · Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, sedatives) as they can increase sedation and respiratory depression risk. · This medication can cause drowsiness; avoid driving or operating heavy machinery until you know how it affects you. · Store at room temperature away from light and moisture. · Keep out of reach of children; accidental ingestion can be fatal. · Do not stop suddenly; your doctor will guide you on tapering if needed. |