ZOHYDRO ER

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZOHYDRO ER (ZOHYDRO ER).

How it works

Zohydro ER is a pure opioid agonist with relative selectivity for mu-opioid receptors, although it can interact with other opioid receptors at higher doses. Its primary therapeutic action is analgesia via binding to mu-opioid receptors in the central nervous system, leading to activation of descending inhibitory pathways and modulation of pain perception.

What the body does with it

Metabolism	Hydrocodone is primarily metabolized by CYP3A4 and CYP2D6. CYP3A4 is the major enzyme responsible for N-demethylation to norhydrocodone, while CYP2D6 mediates O-demethylation to hydromorphone, a more potent opioid metabolite.
Excretion	Primarily renal excretion of hydromorphone-3-glucuronide (H3G, ~60%), unchanged hydromorphone (~15%), and other conjugates. Fecal excretion accounts for ~25%.
Half-life	Terminal elimination half-life is approximately 10.6 hours (range 8-17 hours) due to extended-release formulation; immediate-release hydromorphone half-life is 2-3 hours. Clinically, steady-state is achieved after 3-5 days of dosing.
Protein binding	Approximately 20-30% bound to plasma proteins (albumin). Low binding minimizes drug interactions from protein displacement.
Volume of Distribution	Volume of distribution (Vd) is approximately 3.5 L/kg (range 2-5 L/kg), indicating extensive tissue distribution beyond total body water.
Bioavailability	Oral bioavailability is ~50% (range 40-60%) due to first-pass metabolism; extended-release formulation provides consistent absorption over 12 hours.
Onset of Action	Oral: Onset of analgesia occurs within 1-2 hours due to immediate-release component; peak effect at 3-4 hours.
Duration of Action	Duration of analgesia is 12 hours, allowing twice-daily dosing. Clinical note: Prolonged use may lead to tolerance, requiring dose titration.

Classification & Brands

Dosing & administration

Initial: 20 mg orally every 24 hours; titrate in increments of 10-20 mg every 3-7 days as needed; maximum dose 200 mg every 24 hours.

Dosage form	CAPSULE, EXTENDED RELEASE
Renal impairment	GFR 30-59 mL/min: Initiate at 50% of usual dose and titrate cautiously; GFR <30 mL/min: Not recommended due to accumulation of metabolites.
Liver impairment	Child-Pugh Class A: No adjustment; Child-Pugh Class B: Initiate at 50% of usual dose; Child-Pugh Class C: Not recommended.
Pediatric use	Not approved for pediatric patients; safety and efficacy not established.
Geriatric use	Initiate at 20 mg every 24 hours; titrate cautiously due to increased sensitivity and risk of respiratory depression.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ZOHYDRO ER (ZOHYDRO ER).

Breastfeeding	Hydrocodone is excreted in breast milk with a relative infant dose of approximately 2-3% of maternal weight-adjusted dose. M/P ratio is approximately 1.0. Use with caution; monitor infant for drowsiness, respiratory depression, and poor feeding. Higher risk in CYP2D6 ultra-rapid metabolizers.
Teratogenic Risk	ZOHYDRO ER contains hydrocodone, a Schedule II opioid. First trimester: Increased risk of neural tube defects (OR 2.2) and congenital heart defects (OR 1.8). Second and third trimesters: Chronic use may cause fetal opioid dependence, neonatal abstinence syndrome (NAS), and preterm birth. Avoid use during labor due to risk of neonatal respiratory depression.

Warnings & precautions

■ FDA Black Box Warning

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Significant respiratory depression","Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment","Known or suspected gastrointestinal obstruction, including paralytic ileus","Hypersensitivity to hydrocodone or any other components of the product (e.g., anaphylaxis)"]

Clinical Precautions

Precautions

["Addiction, Abuse, and Misuse","Life-Threatening Respiratory Depression","Neonatal Opioid Withdrawal Syndrome","Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants","Adrenal Insufficiency","Severe Hypotension","Gastrointestinal Effects: Constipation and Risk of Obstruction","Seizures in Patients with Seizure Disorders","Avoidance of Rapid Withdrawal","Driving and Operating Machinery"]

Clinical Tips & Counseling

Drug interactions

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ZOHYDRO ER

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZOHYDRO ER (ZOHYDRO ER).

How it works

What the body does with it

Metabolism	Hydrocodone is primarily metabolized by CYP3A4 and CYP2D6. CYP3A4 is the major enzyme responsible for N-demethylation to norhydrocodone, while CYP2D6 mediates O-demethylation to hydromorphone, a more potent opioid metabolite.
Excretion	Primarily renal excretion of hydromorphone-3-glucuronide (H3G, ~60%), unchanged hydromorphone (~15%), and other conjugates. Fecal excretion accounts for ~25%.
Half-life	Terminal elimination half-life is approximately 10.6 hours (range 8-17 hours) due to extended-release formulation; immediate-release hydromorphone half-life is 2-3 hours. Clinically, steady-state is achieved after 3-5 days of dosing.
Protein binding	Approximately 20-30% bound to plasma proteins (albumin). Low binding minimizes drug interactions from protein displacement.
Volume of Distribution	Volume of distribution (Vd) is approximately 3.5 L/kg (range 2-5 L/kg), indicating extensive tissue distribution beyond total body water.
Bioavailability	Oral bioavailability is ~50% (range 40-60%) due to first-pass metabolism; extended-release formulation provides consistent absorption over 12 hours.
Onset of Action	Oral: Onset of analgesia occurs within 1-2 hours due to immediate-release component; peak effect at 3-4 hours.
Duration of Action	Duration of analgesia is 12 hours, allowing twice-daily dosing. Clinical note: Prolonged use may lead to tolerance, requiring dose titration.

Classification & Brands

Dosing & administration

Initial: 20 mg orally every 24 hours; titrate in increments of 10-20 mg every 3-7 days as needed; maximum dose 200 mg every 24 hours.

Dosage form	CAPSULE, EXTENDED RELEASE
Renal impairment	GFR 30-59 mL/min: Initiate at 50% of usual dose and titrate cautiously; GFR <30 mL/min: Not recommended due to accumulation of metabolites.
Liver impairment	Child-Pugh Class A: No adjustment; Child-Pugh Class B: Initiate at 50% of usual dose; Child-Pugh Class C: Not recommended.
Pediatric use	Not approved for pediatric patients; safety and efficacy not established.
Geriatric use	Initiate at 20 mg every 24 hours; titrate cautiously due to increased sensitivity and risk of respiratory depression.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ZOHYDRO ER (ZOHYDRO ER).

Breastfeeding	Hydrocodone is excreted in breast milk with a relative infant dose of approximately 2-3% of maternal weight-adjusted dose. M/P ratio is approximately 1.0. Use with caution; monitor infant for drowsiness, respiratory depression, and poor feeding. Higher risk in CYP2D6 ultra-rapid metabolizers.
Teratogenic Risk	ZOHYDRO ER contains hydrocodone, a Schedule II opioid. First trimester: Increased risk of neural tube defects (OR 2.2) and congenital heart defects (OR 1.8). Second and third trimesters: Chronic use may cause fetal opioid dependence, neonatal abstinence syndrome (NAS), and preterm birth. Avoid use during labor due to risk of neonatal respiratory depression.