ORALTAG

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ORALTAG (ORALTAG).

How it works

Naloxegol is a PEGylated naloxol derivative that acts as a peripherally acting mu-opioid receptor antagonist. It blocks opioid binding at mu-receptors in the gastrointestinal tract, reversing opioid-induced constipation without compromising central analgesia due to limited blood-brain barrier penetration.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 with minor contribution from CYP2D6. Naloxegol is a substrate of P-glycoprotein (P-gp).
Excretion	Primarily renal excretion of unchanged drug (approx. 70%) and its glucuronide conjugate (approx. 20%); biliary/fecal elimination accounts for <10%.
Half-life	Terminal elimination half-life is approximately 8-12 hours in adults with normal renal function; prolonged to 15-30 hours in renal impairment (CrCl <30 mL/min).
Protein binding	Approximately 75-85% bound primarily to alpha-1-acid glycoprotein (AAG), with minor binding to albumin.
Volume of Distribution	4-6 L/kg, indicating extensive tissue distribution; higher Vd in elderly and patients with hepatic cirrhosis.
Bioavailability	Oral: 40-50% (first-pass metabolism); sublingual: 70-80%; rectal: 50-60%; intravenous: 100%.
Onset of Action	Oral: 30-60 minutes; sublingual: 15-30 minutes; intravenous: immediate (within 1-2 minutes).
Duration of Action	4-6 hours following a single oral dose; 3-5 hours after intravenous administration; clinical analgesia persists for 2-3 hours post-peak effect.

Classification & Brands

Dosing & administration

IV: 4 mg/kg every 12 hours; Oral: 10 mg/kg every 12 hours, max 400 mg/dose.

Dosage form	FOR SOLUTION
Renal impairment	GFR 30-59 mL/min: Reduce dose by 50%; GFR <30 mL/min: Increase dosing interval to every 24 hours.
Liver impairment	Child-Pugh A: No adjustment; Child-Pugh B: Reduce dose by 25%; Child-Pugh C: Avoid use.
Pediatric use	IV: 2-4 mg/kg every 12 hours; Oral: 10-15 mg/kg every 12 hours, max 400 mg/dose.
Geriatric use	Start at lower end of dosing range; monitor renal function; no specific dose adjustment based on age alone.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ORALTAG (ORALTAG).

Breastfeeding	Excreted in human milk; M/P ratio not determined. Potential for hypoglycemia in infant. Use with caution, monitor infant blood glucose.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: potential for congenital malformations based on animal data; human data limited. Second and third trimesters: risk of fetal hypoglycemia and growth restriction due to maternal metabolic effects. Avoid use unless benefit outweighs risk.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known or suspected GI obstruction","Patients at risk of recurrent GI obstruction","Concurrent use with strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, itraconazole, ritonavir)"]

Clinical Precautions

Precautions

["GI perforation: Use with caution in patients with underlying GI lesions or conditions that may increase risk of perforation (e.g., Crohn's disease, peptic ulcer, Ogilvie's syndrome). Discontinue if severe abdominal pain or symptoms of perforation develop.","Opioid withdrawal: May precipitate opioid withdrawal symptoms (e.g., diaphoresis, chills, diarrhea, abdominal pain, anxiety, irritability, yawning). Use with caution in patients with disruption of blood-brain barrier or on higher opioid doses.","Severe hepatic impairment: Not recommended (Child-Pugh Class C).","Drug interactions: Avoid concomitant use with strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) and strong CYP3A4 inducers (e.g., rifampin, carbamazepine)."]

Clinical Tips & Counseling

Drug interactions

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ORALTAG

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ORALTAG (ORALTAG).

How it works

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 with minor contribution from CYP2D6. Naloxegol is a substrate of P-glycoprotein (P-gp).
Excretion	Primarily renal excretion of unchanged drug (approx. 70%) and its glucuronide conjugate (approx. 20%); biliary/fecal elimination accounts for <10%.
Half-life	Terminal elimination half-life is approximately 8-12 hours in adults with normal renal function; prolonged to 15-30 hours in renal impairment (CrCl <30 mL/min).
Protein binding	Approximately 75-85% bound primarily to alpha-1-acid glycoprotein (AAG), with minor binding to albumin.
Volume of Distribution	4-6 L/kg, indicating extensive tissue distribution; higher Vd in elderly and patients with hepatic cirrhosis.
Bioavailability	Oral: 40-50% (first-pass metabolism); sublingual: 70-80%; rectal: 50-60%; intravenous: 100%.
Onset of Action	Oral: 30-60 minutes; sublingual: 15-30 minutes; intravenous: immediate (within 1-2 minutes).
Duration of Action	4-6 hours following a single oral dose; 3-5 hours after intravenous administration; clinical analgesia persists for 2-3 hours post-peak effect.

Classification & Brands

Dosing & administration

IV: 4 mg/kg every 12 hours; Oral: 10 mg/kg every 12 hours, max 400 mg/dose.

Dosage form	FOR SOLUTION
Renal impairment	GFR 30-59 mL/min: Reduce dose by 50%; GFR <30 mL/min: Increase dosing interval to every 24 hours.
Liver impairment	Child-Pugh A: No adjustment; Child-Pugh B: Reduce dose by 25%; Child-Pugh C: Avoid use.
Pediatric use	IV: 2-4 mg/kg every 12 hours; Oral: 10-15 mg/kg every 12 hours, max 400 mg/dose.
Geriatric use	Start at lower end of dosing range; monitor renal function; no specific dose adjustment based on age alone.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ORALTAG (ORALTAG).

Breastfeeding	Excreted in human milk; M/P ratio not determined. Potential for hypoglycemia in infant. Use with caution, monitor infant blood glucose.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: potential for congenital malformations based on animal data; human data limited. Second and third trimesters: risk of fetal hypoglycemia and growth restriction due to maternal metabolic effects. Avoid use unless benefit outweighs risk.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known or suspected GI obstruction","Patients at risk of recurrent GI obstruction","Concurrent use with strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, itraconazole, ritonavir)"]