DEPODUR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DEPODUR (DEPODUR).

How it works

Morphine sulfate extended-release liposomal injection; morphine is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can interact with other opioid receptors at higher doses. The analgesic effects are mediated by activation of mu-opioid receptors in the central nervous system, leading to modulation of pain pathways.

What the body does with it

Metabolism	Primarily hepatic glucuronidation via UGT2B7 to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G); minor metabolism by sulfation.
Excretion	Morphine is primarily excreted renally, with approximately 90% of the dose eliminated in urine within 24 hours, mainly as morphine-3-glucuronide (M3G, ~50%), morphine-6-glucuronide (M6G, ~10%), and unchanged morphine (~10%). Fecal excretion accounts for less than 10%.
Half-life	The terminal elimination half-life of morphine is approximately 2-4 hours in adults. However, DEPODUR (extended-release liposomal morphine) has a prolonged half-life due to slow release from the liposomal depot, with an effective half-life of about 12-24 hours, supporting once-daily dosing.
Protein binding	Morphine is 30-35% bound to plasma proteins, primarily albumin.
Volume of Distribution	The volume of distribution of morphine is approximately 3-5 L/kg, indicating extensive tissue distribution. For DEPODUR, due to the liposomal encapsulation and epidural administration, Vd is not meaningfully applicable; systemic Vd is similar to morphine after release.
Bioavailability	DEPODUR is administered epidurally; the bioavailability from the epidural space into systemic circulation is approximately 100% (complete absorption), but the drug is intended for local action in the epidural space with slow release into systemic circulation. Oral bioavailability of morphine (not DEPODUR) is 20-40% due to first-pass metabolism.
Onset of Action	DEPODUR is administered via epidural injection. Onset of analgesia occurs within 5-10 minutes, with peak effect at 30-60 minutes.
Duration of Action	Duration of analgesia from a single epidural dose of DEPODUR is approximately 48-72 hours, providing sustained pain relief for postoperative management without the need for repeated dosing.

Classification & Brands

Dosing & administration

Epidural: 5-15 mg as a single dose (morphine sulfate 10 mg/mL extended-release liposome injection).

Dosage form	INJECTABLE, LIPOSOMAL
Renal impairment	GFR <60 mL/min: Use with caution; reduce initial dose by 50% and monitor for respiratory depression. GFR <30 mL/min: Contraindicated.
Liver impairment	Child-Pugh A and B: Use with caution; consider dose reduction by 25-50%. Child-Pugh C: Contraindicated.
Pediatric use	Not recommended for pediatric patients (safety and efficacy not established).
Geriatric use	Use with caution; initiate at lower end of dosing range (5 mg epidurally) and monitor closely for respiratory depression due to increased sensitivity and reduced clearance.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DEPODUR (DEPODUR).

Breastfeeding	Contraindicated due to long half-life and high lipid solubility. M/P ratio not established; risk of infant sedation and withdrawal. Discontinue breastfeeding or drug.
Teratogenic Risk	Pregnancy Category C. First trimester: Associated with Ebstein's anomaly and other cardiovascular defects; also neural tube defects. Second and third trimesters: Risk of neonatal withdrawal syndrome, bradycardia, and hypoglycemia. Use only if benefit outweighs risk.
Fetal Monitoring

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. See full prescribing information for complete boxed warning.

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 morphine or any product components"]

Clinical Precautions

Precautions

["Addiction, abuse, and misuse","Life-threatening respiratory depression","Accidental ingestion","Neonatal opioid withdrawal syndrome","Risks from concomitant use with benzodiazepines or other CNS depressants","Adrenal insufficiency","Severe hypotension","Gastrointestinal effects","Seizures","Withdrawal"]

Clinical Tips & Counseling

Drug interactions

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DEPODUR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DEPODUR (DEPODUR).

How it works

What the body does with it

Metabolism	Primarily hepatic glucuronidation via UGT2B7 to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G); minor metabolism by sulfation.
Excretion	Morphine is primarily excreted renally, with approximately 90% of the dose eliminated in urine within 24 hours, mainly as morphine-3-glucuronide (M3G, ~50%), morphine-6-glucuronide (M6G, ~10%), and unchanged morphine (~10%). Fecal excretion accounts for less than 10%.
Half-life	The terminal elimination half-life of morphine is approximately 2-4 hours in adults. However, DEPODUR (extended-release liposomal morphine) has a prolonged half-life due to slow release from the liposomal depot, with an effective half-life of about 12-24 hours, supporting once-daily dosing.
Protein binding	Morphine is 30-35% bound to plasma proteins, primarily albumin.
Volume of Distribution	The volume of distribution of morphine is approximately 3-5 L/kg, indicating extensive tissue distribution. For DEPODUR, due to the liposomal encapsulation and epidural administration, Vd is not meaningfully applicable; systemic Vd is similar to morphine after release.
Bioavailability	DEPODUR is administered epidurally; the bioavailability from the epidural space into systemic circulation is approximately 100% (complete absorption), but the drug is intended for local action in the epidural space with slow release into systemic circulation. Oral bioavailability of morphine (not DEPODUR) is 20-40% due to first-pass metabolism.
Onset of Action	DEPODUR is administered via epidural injection. Onset of analgesia occurs within 5-10 minutes, with peak effect at 30-60 minutes.
Duration of Action	Duration of analgesia from a single epidural dose of DEPODUR is approximately 48-72 hours, providing sustained pain relief for postoperative management without the need for repeated dosing.

Classification & Brands

Dosing & administration

Epidural: 5-15 mg as a single dose (morphine sulfate 10 mg/mL extended-release liposome injection).

Dosage form	INJECTABLE, LIPOSOMAL
Renal impairment	GFR <60 mL/min: Use with caution; reduce initial dose by 50% and monitor for respiratory depression. GFR <30 mL/min: Contraindicated.
Liver impairment	Child-Pugh A and B: Use with caution; consider dose reduction by 25-50%. Child-Pugh C: Contraindicated.
Pediatric use	Not recommended for pediatric patients (safety and efficacy not established).
Geriatric use	Use with caution; initiate at lower end of dosing range (5 mg epidurally) and monitor closely for respiratory depression due to increased sensitivity and reduced clearance.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DEPODUR (DEPODUR).

Breastfeeding	Contraindicated due to long half-life and high lipid solubility. M/P ratio not established; risk of infant sedation and withdrawal. Discontinue breastfeeding or drug.
Teratogenic Risk	Pregnancy Category C. First trimester: Associated with Ebstein's anomaly and other cardiovascular defects; also neural tube defects. Second and third trimesters: Risk of neonatal withdrawal syndrome, bradycardia, and hypoglycemia. Use only if benefit outweighs risk.
Fetal Monitoring