Dose:  10 mg/kg/dose PO or PR (40 mg/kg/day maximum)
            IV: 10 mg/kg as loading dose with a 5 mg/kg dose 24 and 48 hours after the
                   loading dose

Frequency: Q 8 hours PO

Comments: Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). It has both analgesic and antipyretic effects. It does not depress ventilatory drive. NSAIDs act peripherally to interfere with the production and release of prostaglandins and leukotrienes from cellular stores. Since NSAIDs do not block pain receptors directly, the drugs have no effect on chemical mediators already released. To ensure adequate pain relief, the NSAIDs should be administered about an hour prior to the painful procedure and then on a regular interval to prevent emergence of pain. More   comments on ibuprofen.

Recent studies have shown ibuprofen lysine when given IV is as effective as indomethacin IV for the treatment of PDAs.   Though oral dosing of ibuprofen may also be effective in closing PDAs, pharmacokinetic studies have shown much lower peak levels are obtained when a 10 mg/kg dose is given orally compared to IV administration (oral ibuprofen to treat PDAs). Compared to IV indomethacin, IV ibuprofen lysine does not decrease cerebral blood flow and may improve cerebral autoregulation. It does not have any effect on decreasing the incidence of IVH. IV ibuprofen lysine is also less likely to cause oliguria. There is controvery about replacing indomethacin with ibuprofen for the treatment of PDAs. Prophylactic use of ibuprofen lysine has been associated with an increase in chronic lung disease and pulmonary hypertension. However another meta-analysis found that ibuprofen had a slightly superior therapeutic index.   The usual course of treatment to close a PDA consists of three doses: 10 mg/kg as a loading dose and 5 mg/kg given 24 and 48 hours after the loading dose (Aranda. Sem Perinatol 2006; 30:114-120). If all three doses are ordered initially, an order should be included that the RN should check with the MD or NNP before giving the next dose in case there is an adverse reaction to the ibuprofen.

Toxicity: The most frequent side effect is gastric irritation. Potential side effects particularly after long-term use are due to the inhibition of prostaglandin synthesis. This can include platelet dysfunction, liver toxicity, water retention, hyperkalemia, increased blood pressure, renal toxicity, and gastric hemorrhage. Patients with intravascular volume depletion are at much greater risk of renal dysfunction. A recent report has raised some concern that ibuprofen may compete with bilirubin binding sites on albumin ( J Pediatr 2004; 144:386-88).  
An IV preparation, Ibuprofen-THAM, has been associated with an increased incidence of NEC and PPHN. This has not been reported with Ibuprofen lysine. There is a recent report of spontaneous intestinal perforation following oral administration of ibuprofen in two VLBW infants being treated to close a PDA (Tatli. Acta Paediatr 2004; 93:999-1001).

Preparation:
PO: Ibuprofen (Pediaprofen) is available in a 40 mg/ml suspension. Store at room temperature. Shake well.

IV: Ibuprofen lysine (NeoProfen) is available as 10 mg/ml in 2 ml vials.    No dilution is necessary.  Pharmacy will measure patient specific doses.   The drug is infused over 15 minutes on a pump.   The drug is very irritating to tissues.     Ibuprofen  is not be subject to standard dosing times. The first dose should be given promptly after order is received.

Compatibility:   Ibuprofen lysine is known to be compatible with saline and dextrose containing solutions.     Ibuprofen lysine should not be infused with TPN or lipids. Not compatible with dopamine (communication from Ovation Pharm). No other compatibility information is available for other drugs for this newly approved agent as of 4/2007.