NeoProfen

Agents used for Closure of a Patent Ductus Arteriosus

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Do NOT administer by IM injection or by IV bolus.
Administration via an umbilical arterial line has not been evaluated.
 
Reconstitution:
Each ml has 17.1 mg of ibuprofen lysine, which is equivalent to 10 mg/mL of ibuprofen. The recommended dose is 10 mg/kg of ibuprofen. Dilute with dextrose or saline to an appropriate volume.
Discard any remaining solution after the initial withdrawal from the vial, as this product is preservative free.
 
Intravenous infusion:
Administer within 30 minutes of preparation.
Administer via the IV port that is nearest the insertion site.
Infuse over 15 minutes.
Avoid extravasation, as the drug may be irritating to extravascular tissue.
Do not simultaneously administer in the same intravenous line with Total Parenteral Nutrition (TPN). TPN should be interrupted for a 15-minute period before and after drug administration. Maintain line patency by using dextrose or saline.

intraventricular hemorrhage / Delayed / 29.0-29.0
apnea / Delayed / 28.0-28.0
enterocolitis / Delayed / 22.0-22.0
renal failure (unspecified) / Delayed / 1.0-1.0
seizures / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
oliguria / Early / Incidence not known
GI perforation / Delayed / Incidence not known
ileus / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
pulmonary hypertension / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known

anemia / Delayed / 32.0-32.0
hyperuricemia / Delayed / 7.0-7.0
edema / Delayed / 4.0-4.0
hematuria / Delayed / 1.0-1.0
sinus tachycardia / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
hyperglycemia / Delayed / Incidence not known
bleeding / Early / Incidence not known
prolonged bleeding time / Delayed / Incidence not known
gastritis / Delayed / Incidence not known
skin ulcer / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known

gastroesophageal reflux / Delayed / Incidence not known
injection site reaction / Rapid / Incidence not known
skin irritation / Early / Incidence not known
infection / Delayed / Incidence not known

NeoProfen

Rx

IV propionic acid NSAID
For pharmacological closure of patent ductus arteriosus (PDA) in preterm infants
Similar efficacy to IV indomethacin; may have less adverse effects on cerebral, mesenteric, and renal circulation; long term effects not assessed.

Initially, 10 mg/kg IV followed, if necessary, by 2 doses of 5 mg/kg IV at 24-hour intervals. Base all doses on birth weight. Dose should be held in cases of oliguria (< 0.6 ml/kg/hour) or anuria. If the ductus arteriosus fails to close or reopens, a second course of ibuprofen lysine, alternative pharmacological therapy, or surgical closure may be necessary.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Use is contraindicated in patients with significant renal impairment; specific guidelines for dosage adjustments in renal impairment are not available.

Alprostadil: (Contraindicated) As ibuprofen lysine is used for the pharmacologic closure of patent ductus arteriosus (PDA), do not administer to patients who require alprostadil injection for dilation of the ductus arteriosus for oxygenation and perfusion. Alprostadil injection for pediatric use (Prostin VR) has been used with the standard therapy for neonates with restricted pulmonary or systemic blood flow which includes antibiotics (e.g., penicillin and gentamicin), vasopressors (e.g., dopamine, isoproterenol), cardiac glycosides, and diuretics (e.g., furosemide).
Amikacin: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Aminoglycosides: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Gentamicin: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Loop diuretics: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Nonsteroidal antiinflammatory drugs: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Paromomycin: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Plazomicin: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Potassium-sparing diuretics: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Streptomycin: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Thiazide diuretics: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Tobramycin: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.

Ibuprofen Lysine/NeoProfen Intravenous Inj Sol: 1mL, 17.1mg

Safe and effective use has not been established.

Safe and effective use has not been established.

Safe and effective use has not been established.

Safe and effective use has not been established.

Safe and effective use has not been established.
Premature neonates (<= 32 weeks gestation): 10 mg/kg/day IV.

The exact mechanism by which ibuprofen lysine causes closure of a patent ductus arteriosus (PDA) in neonates is not known. However, it is thought that the inhibition of prostaglandin synthesis is relevant. Local release of prostaglandins results in the dilation of, and may delay the closure of, the ductus. Ibuprofen blocks arachidonate binding resulting in competitive inhibition of both cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, which in turn limits the COX-1 and COX-2 catalyzed conversion of arachidonic acid to prostaglandin G2 (PGG2) and subsequent prostaglandin and thromboxane synthesis. Based on in vitro information, ibuprofen has about equal inhibitory effects on COX-1 and COX-2.

Ibuprofen lysine is administered as an intravenous infusion. Pharmacokinetic data were obtained from 54 premature infants included in a double-blind, placebo-controlled, randomized, multicenter study. The infants were less than 30 weeks gestational age, weighed 500—1000 g, and exhibited asymptomatic PDA with echocardiographic documentation of ductal shunting. The study measured the average clearance and volume of distribution values of racemic ibuprofen at birth to be 3 mL/kg/hour and 320 mL/kg, respectively. Clearance increased rapidly with postnatal age (an average increase of approximately 0.5 mL/kg/hour per day). Inter-individual variability in clearance and volume of distribution were 55% and 14%, respectively. In general, the half-life in infants is estimated to be more than 10 times longer than in adults. Metabolism and excretion in premature infants have not been studied. In adults, ibuprofen is metabolized via hepatic oxidation by cytochrome P450 2C9 to two inactive metabolites then excreted in the urine; 50—60% as metabolites and approximately 10% as unchanged drug. Some biliary excretion may occur. Renal function and the enzymes associated with drug metabolism, in general, are underdeveloped at birth and substantially increase in the days after birth.
 
Affected cytochrome P450 isoenzymes: CYP2C9

Ibuprofen lysine is indicated for use in premature neonates only; it should not be used during pregnancy.

Ibuprofen lysine is indicated for use in premature neonates only; do not use in breast-feeding women. Acetaminophen and ibuprofen, products intended for use in adult patients, are both considered to be usually compatible with breast-feeding by the American Academy of Pediatrics (AAP) and may be appropriate alternatives.