DrugindexOnline^{2nd edition}

Pronouncation: (EYE-bue-PROE-fen lye-SEEN)
Class: Patent ductus arteriosus agent

Trade Names:
Neoprofen
- Solution for injection 17.1 mg/mL

Mechanism of Action

Pharmacology

Mechanism by which ibuprofen closes patent ductus arteriosus (PDA) is not known.

In adults, ibuprofen is a prostaglandin synthesis inhibitor.

Pharmacokinetics

Distribution

Population Vd of racemic ibuprofen for premature infants at birth is 320 mL/kg.

Metabolism

Metabolism in premature infants has not been studied.

Elimination

Excretion in premature infants has not been studied. The t _½ in infants is more than 10 times longer than in adults. Interindividual variability in Cl and Vd are 55% and 14%, respectively.

Indications and Usage

Closure of PDA in premature infants weighing between 500 and 1,500 g, who are more than 32 wk gestational age.

Contraindications

Preterm infants with 1) proven or suspected infection that is untreated; 2) congenital heart disease in whom patency of the PDA is necessary for satisfactory pulmonary or systemic blood flow (eg, pulmonary atresia); 3) thrombocytopenia; 4) coagulation defects; 5) suspected necrotizing enterocolitis; 6) significant renal function impairment; or 7) bleeding, especially those with active intracranial hemorrhage or GI bleeding.

Dosage and Administration

Infants

IV A course of therapy is 3 doses. The initial dose of 10 mg/kg is followed by 2 doses of 5 mg/kg after 24 and 48 h.

General Advice

• Base dosage on birth weight.
• If anuria or marked oliguria (urinary output less than 0.6 mL/kg/h) is evident at the time of the scheduled second or third dose, do not give an additional dose until laboratory studies indicate that renal function has returned to normal.
• If ductus arteriosus closes or is significantly reduced in size after completion of first course of treatment, no further doses are necessary.
• If, during continued medical management, the ductus arteriosus fails to close or reopens, a second course of treatment, alternative pharmacological therapy, or surgery may be necessary.
• Inspect the product visually for particulate matter and discoloration prior to administration.
• Dilute the medication to an appropriate volume with dextrose or saline.
• Prepare the infusion for administration within 30 min of administration and infuse continuously over 15 min.
• Administer via the IV port nearest to the insertion site.
• Because the product contains no preservative, discard any remaining solution after the first withdrawal from the vial.
• Do not administer in the same IV line with TPN.
• Interrupt TPN for a 15-min period prior to and after drug administration.
• Maintain line patency with dextrose or saline.

Storage/Stability

Store at 68° to 77°F. Protect from light. Store vials in carton until contents have been used.

Drug Interactions

None well documented in neonates.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Cardiac failure, hypotension, tachycardia.

CNS

Seizures.

Dermatologic

Skin lesion/irritation (16%).

GI

Nonnecrotizing enterocolitis (22%); abdominal distension, gastritis, gastroesophageal reflux, ileus.

Genitourinary

UTI (9%); renal function impairment (6%); reduced urine output (3%); hematuria, renal failure (1%).

Hematologic-Lymphatic

Anemia (32%); intraventricular hemorrhage (IVH) grades 1/2, IVH grades 3/4 (15%); other bleeding (6%); neutropenia, thrombocytopenia.

Hepatic

Cholestasis, jaundice.

Lab Tests

Hypernatremia, increased blood urea (7%); increased blood creatinine (3%).

Local

Injection-site reactions.

Metabolic-Nutritional

Hypocalcemia, hypoglycemia (12%); hyperglycemia.

Respiratory

Apnea (28%); respiratory tract infection (19%); respiratory failure (10%); atelectasis (4%).

Miscellaneous

Sepsis (43%); adrenal insufficiency (7%); edema (4%); feeding problems, infections, inguinal hernia.

Precautions

Bilirubin

Because ibuprofen may displace bilirubin from albumin-binding sites, use with caution in infants with elevated total bilirubin.

Extravasation

Because the solution may be irritating to tissue, administer carefully to avoid extravascular injection or leaking.

Infection

Signs of infection may be altered; use the drug with extra care in presence of controlled infection and in infants at risk of infection.

Platelet function

May inhibit platelet aggregation and prolong bleeding time.

Overdosage

Symptoms

Breathing difficulties, coma, drowsiness, irregular heartbeat, kidney failure, low BP, seizures, vomiting.