Ibuprofen Lysine Drug Information
Generic name: IBUPROFEN LYSINE
Uses of Ibuprofen Lysine
Ibuprofen Lysine 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. Ibuprofen Lysine is a nonsteroidal anti-inflammatory drug 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 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.
Dosage & Administration of Ibuprofen Lysine
Recommended Dose
A course of therapy is three doses of Ibuprofen Lysine 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 Ibuprofen Lysine, 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 Ibuprofen Lysine, no further doses are necessary. If during continued medical management the ductus arteriosus fails to close or reopens, then a second course of Ibuprofen Lysine, 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 Ibuprofen Lysine if particulate matter is observed. After the first withdrawal from the vial, any solution remaining must be discarded because Ibuprofen Lysine contains no preservative.
For administration, Ibuprofen Lysine should be diluted to an appropriate volume with dextrose or saline. Ibuprofen Lysine 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 Ibuprofen Lysine contains no preservative. Since Ibuprofen Lysine is potentially irritating to tissues, it should be administered carefully to avoid extravasation. Ibuprofen Lysine 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.
Side Effects of Ibuprofen Lysine
Clinical Trials Experience
The most frequently reported adverse events with Ibuprofen Lysine were as shown in Table 1. Table 1. Adverse Events within 30 Days of Therapy in the Multicenter Study Within 30 days of therapy, with an event rate greater on Ibuprofen Lysine than on placebo, and greater than 2 events on Ibuprofen Lysine. % Incidence Adverse Event Ibuprofen Lysine Placebo Sepsis 43 37 Anemia 32 25 Total Bleeding A given subject may have experienced more than one specific event within these adverse event categories. Only the most severe grade of IVH counted for a given subject. 32 29 Intraventricular Hemorrhage, Grades 1/2 15 13 Intraventricular Hemorrhage, Grades 3/4 15 10 Other Bleeding 6 13 Intraventricular Hemorrhage, All Grades 29 24 Apnea 28 26 Gastrointestinal Disorders 22 18 non-Necrotizing Enterocolitis Total Renal Events 21 15 Renal Failure 1 3 Renal Insufficiency, Impairment 6 4 Urine Output Reduced 3 1 Blood Creatinine Increased 3 1 Blood Urea Increased with Hematuria 1 1 Blood Urea Increased 7 4 Respiratory Infection 19 13 Skin Lesion/Irritation 16 6 Hypoglycemia 12 6 Hypocalcemia 12 9 Respiratory Failure 10 4 Urinary Tract Infection 9 4 Adrenal Insufficiency 7 1 Hypernatremia 7 4 Edema 4 0 Atelectasis 4 1
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
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 adverse reactions have been identified from spontaneous post-marketing reports or published literature: gastrointestinal perforation, necrotizing enterocolitis, drug reaction with eosinophilia and systemic symptoms (DRESS), and pulmonary hypertension.
Warnings & Cautions for Ibuprofen Lysine
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 Ibuprofen Lysine 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 Ibuprofen Lysine, 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 Ibuprofen Lysine should be administered carefully to avoid extravascular injection or
leakage, as solution may be irritating to tissue.
Serious Skin Reactions
NSAIDS, including ibuprofen, can cause serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), which can be fatal. Ibuprofen should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
Drug Interactions with Ibuprofen Lysine
- 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.
- Diuretics: Increased risk of renal dysfunction.
Contraindications for Ibuprofen Lysine
- Ibuprofen Lysine 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.
- Ibuprofen Lysine is contraindicated in preterm infants: With proven or suspected infection that is untreated With congenital heart disease in whom patency of the PDA is necessary for satisfactory pulmonary or systemic blood flow With impaired renal function With thrombocytopenia, coagulation defects or who are bleeding With or who are suspected of having necrotizing enterocolitis
Overdosage Information for Ibuprofen Lysine
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. The patient should be followed for several days because gastrointestinal ulceration and hemorrhage may occur.
Clinical Studies of Ibuprofen Lysine
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. 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 (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 required rescue therapy versus 48% of infants on placebo (p=0.003 from logistic regression controlling for site). Table 2. Summary of Efficacy Results, n (%) Ibuprofen Lysine N=68 Placebo N=68 Required rescue through study day 14 Total 17 33 By age at treatment Birth to < 24 hours 3/14 8/16 24-48 hours 9/32 16/37 > 48 hours 5/22 9/15 Echocardiographically proven PDA prior to rescue 17 32 Reasons for Rescue Hemodynamically significant PDA per neonatologist 14 25 Bounding pulse 6 12 Systolic murmur 6 15 Pulmonary Edema 3 5 Hyperdynamic precordium 2 3 Increased cardiac silhouette 1 5 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 and placebo groups for mean age at start of first rescue treatment (8.7 days, range 4-15 days, for the Ibuprofen Lysine 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.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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