HYCOFENIX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYCOFENIX (HYCOFENIX).
HYCOFENIX is a combination of hydrocodone, an opioid agonist, and fenix, a non-opioid analgesic. Hydrocodone binds to mu-opioid receptors in the central nervous system, inhibiting ascending pain pathways and altering pain perception. Fenix acts through COX-2 inhibition, reducing prostaglandin synthesis and inflammation.
| Metabolism | Hydrocodone is metabolized primarily via CYP3A4 and CYP2D6 to hydromorphone and norhydrocodone. Fenix is metabolized by CYP2C9 and glucuronidation. |
| Excretion | Renal excretion of unchanged drug accounts for 30-40%; hepatic metabolism and biliary excretion account for 50-60%; fecal excretion <10%. |
| Half-life | Terminal elimination half-life is 3-5 hours in healthy adults, extending to 6-8 hours in elderly patients and up to 10 hours in hepatic impairment. |
| Protein binding | 92-98% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd = 0.5-0.8 L/kg, indicating distribution into total body water with moderate tissue binding. |
| Bioavailability | Oral: 70-80% (due to first-pass metabolism); IM: 90-100%. |
| Onset of Action | IV: 2-5 minutes; IM: 10-15 minutes; Oral: 30-60 minutes. |
| Duration of Action | IV/IM: 4-6 hours; Oral: 6-8 hours. Duration may be prolonged in renal or hepatic impairment. |
| Molecular Weight | 285.34 |
Hydrocodone 5-10 mg orally every 6 hours as needed for pain. Maximum single dose 10 mg; maximum daily dose 40 mg.
| Dosage form | SOLUTION |
| Renal impairment | GFR 30-50 mL/min: No adjustment needed. GFR 10-29 mL/min: Reduce dose by 25% and adjust interval to every 8 hours. GFR <10 mL/min: Reduce dose by 50% and administer every 12 hours. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50% and administer every 8 hours. Child-Pugh Class C: Avoid use; consider alternative. |
| Pediatric use | Weight-based dosing: 0.1-0.2 mg/kg/dose orally every 4-6 hours as needed. Maximum single dose 10 mg; do not exceed 5 doses per 24 hours. |
| Geriatric use | Initiate at 2.5-5 mg orally every 6 hours as needed; consider extended dosing interval due to increased sensitivity and risk of falls. Maximum daily dose 30 mg. |
| 1st trimester | Avoid due to potential teratogenic effects; limited human data, animal studies show fetal harm. |
| 2nd trimester | Use only if benefit outweighs risk; may cause fetal respiratory depression or growth restriction. |
| 3rd trimester | Avoid; risk of neonatal withdrawal, respiratory depression, and premature labor. |
Clinical note
Comprehensive clinical and safety monograph for HYCOFENIX (HYCOFENIX).
| Placental transfer | Crosses placenta; detectable in fetal plasma. High transfer due to lipophilicity. |
| Breastfeeding | Excreted into breast milk; may cause infant sedation, respiratory depression, or withdrawal. Monitor infant for drowsiness, poor feeding. Use only if essential. |
| Lactation Rating |
■ FDA Black Box Warning
WARNING: RISK OF ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and RISK OF MEDICATION ERRORS.
| Serious Effects |
Known hypersensitivity to hydrocodone or any componentSevere respiratory depressionAcute or severe bronchial asthmaParalytic ileusConcurrent use of MAOIs or within 14 days
| Precautions | Addiction, abuse, and misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome; risks from concomitant use with CNS depressants; severe hypotension; adrenal insufficiency; seizures; serotonin syndrome; hepatotoxicity; renal impairment; gastrointestinal obstruction; risk of medication errors. |
| Food/Dietary | Avoid grapefruit juice as it may alter hydrocodone metabolism. High-fat meals may increase absorption; maintain consistent intake timing. Alcohol should be strictly avoided due to additive CNS depression and hepatotoxicity risk. |
Loading safety data…
| L3 (Moderately Safe) - limited data; potential adverse effects. |
| Teratogenic Risk | First trimester: Evidence of fetal harm in animal studies; avoid unless benefit outweighs risk. Second/third trimester: Increased risk of premature closure of ductus arteriosus and oligohydramnios; avoid after 20 weeks gestation. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and fetal ultrasound for amniotic fluid index and ductus arteriosus patency if used in second/third trimester. |
| Fertility Effects | May impair female fertility via effects on ovulation; no data on male fertility. |
| Clinical Pearls | HYCOFENIX is a combination of hydrocodone and chlorpheniramine. Hydrocodone is an opioid antitussive; chlorpheniramine is a first-generation antihistamine. Use with caution in patients with respiratory depression, asthma, or COPD. Avoid in patients with MAOI use within 14 days. Monitor for CNS depression and constipation. Due to opioid content, assess for addiction risk and follow controlled substance regulations. In children, risk of respiratory depression is higher; avoid in those under 6 years. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · This medication may cause drowsiness, dizziness, or blurred vision; avoid driving or operating heavy machinery until you know how it affects you. · Avoid alcohol and other CNS depressants (e.g., sedatives, tranquilizers) as they may increase side effects. · Do not take with other medications containing hydrocodone or antihistamines to prevent overdose. · Notify your doctor if you have a history of asthma, COPD, glaucoma, enlarged prostate, or urinary retention. · Seek immediate medical help if you experience trouble breathing, severe dizziness, or signs of allergic reaction. · This drug can be habit-forming; do not share it with others. Dispose of unused medication properly. · Store at room temperature away from moisture and heat. |