NEOPROFEN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NEOPROFEN (NEOPROFEN).

How it works

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis and thereby decreasing inflammation, pain, and fever.

What the body does with it

Metabolism	Ibuprofen is primarily metabolized in the liver by cytochrome P450 enzymes, mainly CYP2C9, to inactive metabolites.
Excretion	Ibuprofen is primarily excreted renally as metabolites (approximately 90% of the dose), with less than 1% excreted unchanged. A small fraction (≤10%) is eliminated via bile/feces. For Neoprofen (ibuprofen lysine specifically used for patent ductus arteriosus), renal excretion accounts for >90% of elimination, predominantly as glucuronide conjugates and hydroxylated metabolites.
Half-life	Terminal elimination half-life is approximately 2.5 to 4 hours in adults. In preterm neonates (target population for Neoprofen), half-life is prolonged due to immature renal function: mean 30.5 hours (range 20–50 hours) after first dose, decreasing to ~15 hours after third dose. Clinical relevance: requires careful dosing intervals in neonates to avoid accumulation.
Protein binding	Ibuprofen is highly protein bound (>99%), primarily to albumin. In neonates, lower albumin concentrations may result in slightly higher free fraction, but binding remains extensive.
Volume of Distribution	Volume of distribution in adults: 0.1–0.2 L/kg. In preterm neonates: higher Vd, approximately 0.2–0.4 L/kg, reflecting larger extracellular fluid volume. Clinical meaning: distributes primarily in central compartment; high Vd in neonates suggests need for loading dose.
Bioavailability	Neoprofen is administered intravenously, giving 100% bioavailability. Oral bioavailability of ibuprofen is >80% but not applicable for this IV formulation.
Onset of Action	Intravenous administration (IV): Onset of action for ductal closure typically occurs within 24–48 hours after the first dose, with full effect often requiring three doses. Analgesic/antipyretic effects from IV ibuprofen occur within 30 minutes. Oral (not applicable for Neoprofen formulation): N/A.
Duration of Action	Duration of ductal closure effect is sustained if closure achieved; if incomplete, further doses may be needed. Antipyretic/analgesic duration from a single IV dose is approximately 4–6 hours. In preterm neonates, hemodynamic effects (ductal constriction) persist for several hours after each infusion.

Classification & Brands

Dosing & administration

IV: 10 mg/kg over 15 minutes, followed by 5 mg/kg at 24, 48, and 72 hours after the first dose.

Dosage form	INJECTABLE
Renal impairment	CrCl 30-89 mL/min: No adjustment. CrCl <30 mL/min: Consider reducing total dose by 50%.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B or C: Avoid use; data lacking.
Pediatric use	Neonates (postmenstrual age >37 weeks): IV: 10 mg/kg initial dose, then 5 mg/kg at 24 and 48 hours for closure of patent ductus arteriosus. Infants >2 years: Not established.
Geriatric use	No specific dose adjustment; use caution due to increased risk of renal and gastrointestinal effects.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for NEOPROFEN (NEOPROFEN).

Breastfeeding	Ibuprofen is excreted into breast milk in low amounts (M/P ratio 0.05-0.33). The relative infant dose is less than 1% of the maternal weight-adjusted dose. Considered compatible with breastfeeding; however, avoid in preterm infants or those with renal impairment.
Teratogenic Risk	Neoprofen (ibuprofen) is contraindicated during pregnancy, especially during the third trimester due to the risk of premature closure of the ductus arteriosus and oligohydramnios. First trimester use may be associated with an increased risk of miscarriage and congenital malformations (cardiac defects, gastroschisis). Second trimester use should be avoided unless clearly necessary.

Warnings & precautions

■ FDA Black Box Warning

Risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal; risk increases with duration of use and in patients with cardiovascular risk factors. Also, risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of stomach or intestines.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to ibuprofen or any component of the formulation; proven or suspected life-threatening infection; active bleeding or coagulopathy; necrotizing enterocolitis; significant renal impairment; congenital heart disease requiring ductal patency.

Clinical Precautions

Precautions

May cause necrotizing enterocolitis in premature infants; monitor renal function and watch for signs of infection; avoid concurrent use of other NSAIDs; use with caution in neonates with renal impairment, bleeding disorders, or gastrointestinal issues.

Clinical Tips & Counseling

Drug interactions

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NEOPROFEN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NEOPROFEN (NEOPROFEN).

How it works

What the body does with it

Metabolism	Ibuprofen is primarily metabolized in the liver by cytochrome P450 enzymes, mainly CYP2C9, to inactive metabolites.
Excretion	Ibuprofen is primarily excreted renally as metabolites (approximately 90% of the dose), with less than 1% excreted unchanged. A small fraction (≤10%) is eliminated via bile/feces. For Neoprofen (ibuprofen lysine specifically used for patent ductus arteriosus), renal excretion accounts for >90% of elimination, predominantly as glucuronide conjugates and hydroxylated metabolites.
Half-life	Terminal elimination half-life is approximately 2.5 to 4 hours in adults. In preterm neonates (target population for Neoprofen), half-life is prolonged due to immature renal function: mean 30.5 hours (range 20–50 hours) after first dose, decreasing to ~15 hours after third dose. Clinical relevance: requires careful dosing intervals in neonates to avoid accumulation.
Protein binding	Ibuprofen is highly protein bound (>99%), primarily to albumin. In neonates, lower albumin concentrations may result in slightly higher free fraction, but binding remains extensive.
Volume of Distribution	Volume of distribution in adults: 0.1–0.2 L/kg. In preterm neonates: higher Vd, approximately 0.2–0.4 L/kg, reflecting larger extracellular fluid volume. Clinical meaning: distributes primarily in central compartment; high Vd in neonates suggests need for loading dose.
Bioavailability	Neoprofen is administered intravenously, giving 100% bioavailability. Oral bioavailability of ibuprofen is >80% but not applicable for this IV formulation.
Onset of Action	Intravenous administration (IV): Onset of action for ductal closure typically occurs within 24–48 hours after the first dose, with full effect often requiring three doses. Analgesic/antipyretic effects from IV ibuprofen occur within 30 minutes. Oral (not applicable for Neoprofen formulation): N/A.
Duration of Action	Duration of ductal closure effect is sustained if closure achieved; if incomplete, further doses may be needed. Antipyretic/analgesic duration from a single IV dose is approximately 4–6 hours. In preterm neonates, hemodynamic effects (ductal constriction) persist for several hours after each infusion.

Classification & Brands

Dosing & administration

IV: 10 mg/kg over 15 minutes, followed by 5 mg/kg at 24, 48, and 72 hours after the first dose.

Dosage form	INJECTABLE
Renal impairment	CrCl 30-89 mL/min: No adjustment. CrCl <30 mL/min: Consider reducing total dose by 50%.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B or C: Avoid use; data lacking.
Pediatric use	Neonates (postmenstrual age >37 weeks): IV: 10 mg/kg initial dose, then 5 mg/kg at 24 and 48 hours for closure of patent ductus arteriosus. Infants >2 years: Not established.
Geriatric use	No specific dose adjustment; use caution due to increased risk of renal and gastrointestinal effects.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for NEOPROFEN (NEOPROFEN).

Breastfeeding	Ibuprofen is excreted into breast milk in low amounts (M/P ratio 0.05-0.33). The relative infant dose is less than 1% of the maternal weight-adjusted dose. Considered compatible with breastfeeding; however, avoid in preterm infants or those with renal impairment.
Teratogenic Risk	Neoprofen (ibuprofen) is contraindicated during pregnancy, especially during the third trimester due to the risk of premature closure of the ductus arteriosus and oligohydramnios. First trimester use may be associated with an increased risk of miscarriage and congenital malformations (cardiac defects, gastroschisis). Second trimester use should be avoided unless clearly necessary.