HYCOFENIX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HYCOFENIX (HYCOFENIX).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for HYCOFENIX (HYCOFENIX).

Breastfeeding	Drug excreted in human milk; M/P ratio unknown. Potential for serious adverse reactions in nursing infants; decide to discontinue nursing or drug based on importance of drug to mother.
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

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to hydrocodone or fenix; significant respiratory depression; acute or severe bronchial asthma; gastrointestinal obstruction; suspected or known paralytic ileus; severe hepatic impairment; concomitant use with MAOIs or within 14 days of such therapy.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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HYCOFENIX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for HYCOFENIX (HYCOFENIX).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for HYCOFENIX (HYCOFENIX).

Breastfeeding	Drug excreted in human milk; M/P ratio unknown. Potential for serious adverse reactions in nursing infants; decide to discontinue nursing or drug based on importance of drug to mother.
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