ZYDONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZYDONE (ZYDONE).

How it works

Hydrocodone is a mu-opioid receptor agonist; acetaminophen produces analgesia via central COX inhibition and activation of descending serotonergic pathways.

What the body does with it

Metabolism	Hydrocodone: CYP3A4 and CYP2D6; acetaminophen: primarily glucuronidation via UGT1A1, UGT1A6, and UGT1A9, with minor oxidation via CYP2E1 and CYP1A2.
Excretion	Approximately 60% of hydrocodone and its metabolites are excreted renally as glucuronide conjugates; ~10% as norhydrocodone, hydromorphone, and other metabolites. Fecal excretion accounts for less than 5%. Total renal elimination: ~65-70%.
Half-life	Terminal elimination half-life of hydrocodone is 3.8-4.5 hours in healthy adults; prolonged in elderly or hepatic impairment (up to 6-8 hours). Clinical context: dosing interval typically every 4-6 hours, adjusted for renal/hepatic insufficiency.
Protein binding	Hydrocodone is approximately 20-30% bound to plasma proteins, primarily albumin.
Volume of Distribution	Hydrocodone has a volume of distribution of approximately 3.5-5.5 L/kg, indicating extensive tissue distribution and sequestration in peripheral compartments.
Bioavailability	Oral bioavailability of hydrocodone is 50-70% due to first-pass metabolism.
Onset of Action	Oral: 10-20 minutes after administration, with peak effect at 30-60 minutes.
Duration of Action	Analgesic duration: 4-6 hours after oral administration. Clinical note: duration may be shorter with single-dose and longer with repeated dosing due to accumulation.

Classification & Brands

Dosing & administration

Oral: 1 to 2 tablets every 4 to 6 hours as needed for pain. Each tablet contains hydrocodone bitartrate 5 mg and acetaminophen 500 mg (Zydone 5/500). Maximum acetaminophen dose: 4000 mg/day (8 tablets).

Dosage form	TABLET
Renal impairment	For CrCl 30-50 mL/min: reduce dose to 50% of normal and extend dosing interval to every 6 hours. For CrCl <30 mL/min: avoid use due to risk of acetaminophen accumulation and hydrocodone toxicity.
Liver impairment	Child-Pugh Class A: no adjustment; Class B: reduce dose by 50% and monitor; Class C: avoid use due to risk of hepatic encephalopathy and toxicity.
Pediatric use	Not recommended for children <18 years due to risk of respiratory depression and lack of safety data.
Geriatric use	Initiate at 50% of adult dose (e.g., 0.5 tablet every 6 hours) and titrate cautiously due to increased sensitivity to opioids and risk of falls, cognitive impairment, and constipation.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ZYDONE (ZYDONE).

Breastfeeding	Excreted into breast milk; M/P ratio approximately 0.8:1. Low absolute infant dose (approx 1-2% of maternal weight-adjusted dose). Monitor infant for sedation, respiratory depression, and withdrawal. Use with caution; alternative agents preferred.
Teratogenic Risk	First trimester: Limited human data; animal studies show increased risk of neural tube defects and skeletal anomalies at maternally toxic doses. Second and third trimesters: Associated with neonatal respiratory depression, withdrawal syndrome, and reduced fetal growth. Risk of preterm birth and low birth weight. Avoid use unless maternal benefit outweighs fetal risk.

Warnings & precautions

■ FDA Black Box Warning

Risk of medication errors (confusion between immediate-release and extended-release products); addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; interactions with alcohol or central nervous system depressants; hepatotoxicity from acetaminophen overdose.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to hydrocodone or acetaminophen, respiratory depression, acute or severe bronchial asthma, GI obstruction, known or suspected paralytic ileus.

Clinical Precautions

Precautions

Respiratory depression, drug dependence, abuse potential, CNS depression, hepatotoxicity (acetaminophen), adrenal insufficiency, hypotension, seizures, severe hypotension, gastrointestinal obstruction, and anaphylaxis.

Clinical Tips & Counseling

Drug interactions

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ZYDONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZYDONE (ZYDONE).

How it works

Hydrocodone is a mu-opioid receptor agonist; acetaminophen produces analgesia via central COX inhibition and activation of descending serotonergic pathways.

What the body does with it

Metabolism	Hydrocodone: CYP3A4 and CYP2D6; acetaminophen: primarily glucuronidation via UGT1A1, UGT1A6, and UGT1A9, with minor oxidation via CYP2E1 and CYP1A2.
Excretion	Approximately 60% of hydrocodone and its metabolites are excreted renally as glucuronide conjugates; ~10% as norhydrocodone, hydromorphone, and other metabolites. Fecal excretion accounts for less than 5%. Total renal elimination: ~65-70%.
Half-life	Terminal elimination half-life of hydrocodone is 3.8-4.5 hours in healthy adults; prolonged in elderly or hepatic impairment (up to 6-8 hours). Clinical context: dosing interval typically every 4-6 hours, adjusted for renal/hepatic insufficiency.
Protein binding	Hydrocodone is approximately 20-30% bound to plasma proteins, primarily albumin.
Volume of Distribution	Hydrocodone has a volume of distribution of approximately 3.5-5.5 L/kg, indicating extensive tissue distribution and sequestration in peripheral compartments.
Bioavailability	Oral bioavailability of hydrocodone is 50-70% due to first-pass metabolism.
Onset of Action	Oral: 10-20 minutes after administration, with peak effect at 30-60 minutes.
Duration of Action	Analgesic duration: 4-6 hours after oral administration. Clinical note: duration may be shorter with single-dose and longer with repeated dosing due to accumulation.

Classification & Brands

Dosing & administration

Dosage form	TABLET
Renal impairment	For CrCl 30-50 mL/min: reduce dose to 50% of normal and extend dosing interval to every 6 hours. For CrCl <30 mL/min: avoid use due to risk of acetaminophen accumulation and hydrocodone toxicity.
Liver impairment	Child-Pugh Class A: no adjustment; Class B: reduce dose by 50% and monitor; Class C: avoid use due to risk of hepatic encephalopathy and toxicity.
Pediatric use	Not recommended for children <18 years due to risk of respiratory depression and lack of safety data.
Geriatric use	Initiate at 50% of adult dose (e.g., 0.5 tablet every 6 hours) and titrate cautiously due to increased sensitivity to opioids and risk of falls, cognitive impairment, and constipation.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ZYDONE (ZYDONE).

Breastfeeding	Excreted into breast milk; M/P ratio approximately 0.8:1. Low absolute infant dose (approx 1-2% of maternal weight-adjusted dose). Monitor infant for sedation, respiratory depression, and withdrawal. Use with caution; alternative agents preferred.
Teratogenic Risk	First trimester: Limited human data; animal studies show increased risk of neural tube defects and skeletal anomalies at maternally toxic doses. Second and third trimesters: Associated with neonatal respiratory depression, withdrawal syndrome, and reduced fetal growth. Risk of preterm birth and low birth weight. Avoid use unless maternal benefit outweighs fetal risk.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to hydrocodone or acetaminophen, respiratory depression, acute or severe bronchial asthma, GI obstruction, known or suspected paralytic ileus.