Ibuprofen Lysine

Ibuprofen Lysine Injection 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.

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

Ibuprofen Lysine Injection 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.

• 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.

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 Ibuprofen Lysine Injection. The patient should be followed for several days because gastrointestinal ulceration and hemorrhage may occur.

Ibuprofen Lysine Injection is a clear sterile preservative-free solution of the L-lysine salt of (±)-ibuprofen which is the active ingredient. (±)-Ibuprofen is a nonsteroidal anti-inflammatory agent (NSAID). L-lysine is used to create a water-soluble drug product salt suitable for intravenous administration. Each mL of Ibuprofen Lysine Injection contains 17.1 mg of ibuprofen lysine (equivalent to 10 mg of (±)-ibuprofen) in Water for Injection, USP. The pH is adjusted to 7.0 with sodium hydroxide or hydrochloric acid.

The structural formula is:

Structural Formula

Ibuprofen Lysine Injection is designated chemically as α-methyl-4-(2-methyl propyl) benzeneacetic acid lysine salt. Its molecular weight is 352.48. Its empirical formula is C ₁₉H ₃₂N ₂O ₄. It occurs as a white crystalline solid which is soluble in water and slightly soluble in ethanol.

In a double-blind, multicenter clinical study premature infants of birth weight between 500 and 1000 g, less than 30 weeks post-conceptional age, and with echocardiographic evidence of a PDA were randomized to placebo or Ibuprofen Lysine Injection. These infants were asymptomatic from their PDA at the time of enrollment. The primary efficacy parameter was the need for rescue therapy (indomethacin, open-label ibuprofen, or surgery) to treat a hemodynamically significant PDA by study day 14. An infant was rescued if there was clinical evidence of a hemodynamically significant PDA that was echocardiographically confirmed. A hemodynamically significant PDA was defined by three of the following five criteria ― bounding pulse, hyperdynamic precordium, pulmonary edema, increased cardiac silhouette, or systolic murmur ― or hemodynamically significant ductus as determined by a neonatologist.

One hundred and thirty-six premature infants received either placebo or Ibuprofen Lysine Injection (10 mg/kg on the first dose and 5 mg/kg at 24 and 48 hours). Mean birth age was 1.5 days (range: 4.6 – 73.0 hours), mean gestational age was 26 weeks (range: 23 – 30 weeks), and mean weight was 798 g (range: 530 – 1015 g).

All infants had a documented PDA with evidence of ductal shunting. As shown in Table 2, 25% of infants on Ibuprofen Lysine Injection required rescue therapy versus 48% of infants on placebo (p=0.003 from logistic regression controlling for site).

Of the infants requiring rescue within the first 14 days after the first dose of study drug, no statistically significant difference was observed between the Ibuprofen Lysine Injection and placebo groups for mean age at start of first rescue treatment (8.7 days, range 4-15 days, for the Ibuprofen Lysine Injection group and 6.9 days, range 2-15 days, for the placebo group).

The groups were similar in the number of deaths by day 14, the number of patients on a ventilator or requiring oxygenation at day 1, 4 and 14, the number of patients requiring surgical ligation of their PDA (12%), the number of cases of Pulmonary Hemorrhage and Pulmonary Hypertension by day 14, and Bronchopulmonary Dysplasia at day 28. In addition, no significant differences were noted in the incidences of Stage 2 and 3 Necrotizing Enterocolitis, Grades 3 and 4 Intraventricular Hemorrhage, Periventricular Leukomalacia and Retinopathy of Prematurity between groups as determined at 36±1 weeks adjusted gestational age.

Two supportive studies also determined that ibuprofen, either prophylactically (n=433, weight range: 400 – 2165 g) or as treatment (n=210, weight range: 400 – 2370 g), was superior to placebo (or no treatment) in preventing the need for rescue therapy for a symptomatic PDA.

How Supplied

Ibuprofen Lysine Injection is dispensed in clear plastic single-use vials, each containing 2 mL of sterile solution (NDC 39822-1030-1). 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. Ibuprofen Lysine Injection is supplied in a carton containing 3 single-use vials (NDC 39822-1030-2).

Storage and Handling

Store at 20 to 25°C (68 to 77°F); excursions permitted 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature]. Protect from light. Store vials in carton until contents have been used.

Infection

Ibuprofen Lysine Injection may alter signs of infection. Patients’ caregivers should be informed to monitor the infant for any signs of infection.

Platelet Aggregation

Patients’ caregivers should be informed that like other NSAIDS, Ibuprofen Lysine Injection can inhibit clot formation therefore their infant should be monitored for any signs of bleeding.

Administration

Patients’ caregivers should be informed that the infants’ skin and tissues should be monitored as leakage from administration may be irritating to tissue.

Manufactured for:

djb logo

XGen Pharmaceuticals DJB, Inc.
Big Flats, NY 14814

rx only

Revised: October 2023
IBUL-PI-09

NDC39822-1030-1

3 x 2 mL Single Use Vials

Ibuprofen Lysine Injection

10 mg/mL

Sterile Solution for IV Use Only
DJB vial

NDC39822-1030-2

3 x 2 mL Single Use Vials

Ibuprofen Lysine Injection

10 mg/mL

djb Carton

Each mL contains:
Ibuprofen 10 mg (as ibuprofen lysine) in Water for Injection, USP.

Dilute to an appropriate volume with dextrose or saline. Please refer to the Package Insert for full prescribing information.

Store at 20-25ºC (68-77ºF); excursions permitted 15-30ºC (59-86ºF). Store vials in carton until use.