NeoProfen

Dosage Forms And Strengths

10 mg/mL as a clear sterile preservative-free solution of the L-lysine salt of ibuprofen in a 2 mL single-use vial.

Storage And Handling

NeoProfen (ibuprofen lysine) Injection is dispensed in treated* clear glass single-use vials, each containing 2 mL of sterile solution (NDC 55292-122-52). The solution is not buffered and contains no preservatives. Each milliliter contains 17.1 mg/mL (±)-ibuprofen L-lysine [equivalent to 10 mg/mL (±)-ibuprofen] dissolved in Water for Injection, USP. NeoProfen is supplied in a carton containing 3 single-use vials.

Storage And Handling

Store at 20 – 25 °C (68 – 77 °F); excursions permitted 15 – 30 °C (59 – 86 °F). Protect from light. Store vials in carton until contents have been used.

*NeoProfen (ibuprofen lysine) Injection is dispensed in a glass vial having a silicon dioxide coating or polymer coating that inhibits the formation of particulates that result from the interaction of the ibuprofen lysine with untreated glass.

Manufactured by: Alcami Carolinas Corporation, Charleston, SC 29405, U.S.A. Revised: Oct 2017

NeoProfen is indicated to close a clinically significant patent ductus arteriosus (PDA) in premature infants weighing between 500 and 1500 g, who are no more than 32 weeks gestational age when usual medical management (e.g., fluid restriction, diuretics, respiratory support, etc.) is ineffective. The clinical trial was conducted among infants with an asymptomatic PDA. However, the consequences beyond 8 weeks after treatment have not been evaluated; therefore, treatment should be reserved for infants with clear evidence of a clinically significant PDA.

Recommended Dose

A course of therapy is three doses of NeoProfen administered intravenously (administration via an umbilical arterial line has not been evaluated). An initial dose of 10 mg per kilogram is followed by two doses of 5 mg per kilogram each, after 24 and 48 hours. All doses should be based on birth weight. If anuria or marked oliguria (urinary output <0.6 mL/kg/hr) is evident at the scheduled time of the second or third dose of NeoProfen, no additional dosage should be given until laboratory studies indicate that renal function has returned to normal. If the ductus arteriosus closes or is significantly reduced in size after completion of the first course of NeoProfen, no further doses are necessary. If during continued medical management the ductus arteriosus fails to close or reopens, then a second course of NeoProfen, alternative pharmacological therapy, or surgery may be necessary.

Directions For Use

For intravenous administration only. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use NeoProfen if particulate matter is observed.

After the first withdrawal from the vial, any solution remaining must be discarded because NeoProfen contains no preservative.

For administration, NeoProfen should be diluted to an appropriate volume with dextrose or saline. NeoProfen should be prepared for infusion and administered within 30 minutes of preparation and infused continuously over a period of 15 minutes. The drug should be administered via the IV port that is nearest the insertion site. After the first withdrawal from the vial, any solution remaining must be discarded because NeoProfen contains no preservative.

Since NeoProfen is potentially irritating to tissues, it should be administered carefully to avoid extravasation.

NeoProfen should not be simultaneously administered in the same intravenous line with Total Parenteral Nutrition (TPN). If necessary, TPN should be interrupted for a 15-minute period prior to and after drug administration. Line patency should be maintained by using dextrose or saline.

NeoProfen is contraindicated in:

• Preterm infants with proven or suspected infection that is untreated;
• Preterm infants with congenital heart disease in whom patency of the PDA is necessary for satisfactory pulmonary or systemic blood flow (e.g., pulmonary atresia, severe tetralogy of Fallot, severe coarctation of the aorta);
• Preterm infants who are bleeding, especially those with active intracranial hemorrhage or gastrointestinal bleeding;
• Preterm infants with thrombocytopenia;
• Preterm infants with coagulation defects;
• Preterm infants with or who are suspected of having necrotizing enterocolitis;
• Preterm infants with significant impairment of renal function.

WARNINGS

Included as part of the "PRECAUTIONS" Section

PRECAUTIONS

General

There are no long-term evaluations of the infants treated with ibuprofen at durations greater than the 36 weeks post-conceptual age observation period. Ibuprofen’s effects on neurodevelopmental outcome and growth as well as disease processes associated with prematurity (such as retinopathy of prematurity and chronic lung disease) have not been assessed.

Infection

NeoProfen may alter the usual signs of infection. The physician must be continually on the alert and should use the drug with extra care in the presence of controlled infection and in infants at risk of infection.

Platelet Aggregation

NeoProfen, like other non-steroidal anti-inflammatory agents, can inhibit platelet aggregation. Preterm infants should be observed for signs of bleeding. Ibuprofen has been shown to prolong bleeding time (but within the normal range) in normal adult subjects. This effect may be exaggerated in patients with underlying hemostatic defects (see CONTRAINDICATIONS).

Bilirubin Displacement

Ibuprofen has been shown to displace bilirubin from albumin binding-sites; therefore, it should be used with caution in patients with elevated total bilirubin.

Administration

NeoProfen should be administered carefully to avoid extravascular injection or leakage, as solution may be irritating to tissue.

Use In Specific Populations

Pediatric Use

Safety and effectiveness have only been established in premature infants.

SIDE EFFECTS

Clinical Trials Experience

The most frequently reported adverse events with NeoProfen were as shown in Table 1.

Table 1. Adverse Events within 30 Days of Therapy in the Multicenter Study*

Renal Function

Compared to placebo, there was a small decrease in urinary output in the ibuprofen group on days 2-6 of life, with a compensatory increase in urine output on day 9. In other studies, adverse events classified as renal insufficiency including oliguria, elevated BUN, elevated creatinine, or renal failure were reported in ibuprofen treated infants.

Additional Adverse Events

The adverse events reported in the multicenter study and of unknown association include tachycardia, cardiac failure, abdominal distension, gastroesophageal reflux, gastritis, ileus, inguinal hernia, injection site reactions, cholestasis, various infections, feeding problems, convulsions, jaundice, hypotension, and various laboratory abnormalities including neutropenia, thrombocytopenia, and hyperglycemia.

Post-Marketing Experience

The following adverse reactions have been identified from spontaneous post-marketing reports or published literature: gastrointestinal perforation, necrotizing enterocolitis, and pulmonary hypertension. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency, or establish a causal relationship to drug exposure.

DRUG INTERACTIONS

• Diuretics

  Ibuprofen may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. Monitor renal function in patients receiving concomitant diuretics.

• Amikacin

  Ibuprofen may decrease the clearance of amikacin.

Clinical Trials Experience

The most frequently reported adverse events with NeoProfen were as shown in Table 1.

Table 1. Adverse Events within 30 Days of Therapy in the Multicenter Study*

Renal Function

Compared to placebo, there was a small decrease in urinary output in the ibuprofen group on days 2-6 of life, with a compensatory increase in urine output on day 9. In other studies, adverse events classified as renal insufficiency including oliguria, elevated BUN, elevated creatinine, or renal failure were reported in ibuprofen treated infants.

Additional Adverse Events

The adverse events reported in the multicenter study and of unknown association include tachycardia, cardiac failure, abdominal distension, gastroesophageal reflux, gastritis, ileus, inguinal hernia, injection site reactions, cholestasis, various infections, feeding problems, convulsions, jaundice, hypotension, and various laboratory abnormalities including neutropenia, thrombocytopenia, and hyperglycemia.

Post-Marketing Experience

The following adverse reactions have been identified from spontaneous post-marketing reports or published literature: gastrointestinal perforation, necrotizing enterocolitis, and pulmonary hypertension. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency, or establish a causal relationship to drug exposure.

The following signs and symptoms have occurred in individuals (not necessarily in premature infants) following an overdose of oral ibuprofen: breathing difficulties, coma, drowsiness, irregular heartbeat, kidney failure, low blood pressure, seizures, and vomiting. There are no specific measures to treat acute overdosage with NeoProfen. The patient should be followed for several days because gastrointestinal ulceration and hemorrhage may occur.