Ibuprofen lysine was developed for the treatment of patent ductus arteriosus (PDA) in premature infants. It is an injectable l-lysine salt of ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID) of the propionic acid chemical class. L-lysine is used to create a water-soluble solution suitable for intravenous administration. In clinical studies, ibuprofen lysine has been shown to be as effective as intravenous indomethacin in closing PDA of premature infants with a success rate of approximately 75%. Ibuprofen appears to be the drug of choice for closing a PDA due to its lower risk of necrotizing enterocolitis (NEC) and transient renal insufficiency compared to indomethacin. Indomethacin is known to result in a marked decrease in blood flow to the cerebral, mesenteric, and renal circulation; echocardiographic study of animal models and preterm infants treated with ibuprofen lysine showed no significant reductions. However, decreases in renal function in some ibuprofen lysine treated neonates were seen in subsequent studies. Long term survival and effect on neurodevelopment have not been assessed. Ibuprofen lysine was approved by the FDA in April 2006 to close clinically significant patent ductus arteriosus in infants weighing 500-1500 grams who are no more than 32 weeks gestational age when usual medical management is ineffective.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Do NOT administer by IM injection or by IV bolus.
-Administration via an umbilical arterial line has not been evaluated.
Reconstitution:
-Each ml has 17.1 mg of ibuprofen lysine, which is equivalent to 10 mg/mL of ibuprofen. The recommended dose is 10 mg/kg of ibuprofen. Dilute with dextrose or saline to an appropriate volume.
-Discard any remaining solution after the initial withdrawal from the vial, as this product is preservative free.
Intravenous infusion:
-Administer within 30 minutes of preparation.
-Administer via the IV port that is nearest the insertion site.
-Infuse over 15 minutes.
-Avoid extravasation, as the drug may be irritating to extravascular tissue.
-Do not simultaneously administer in the same intravenous line with Total Parenteral Nutrition (TPN). TPN should be interrupted for a 15-minute period before and after drug administration. Maintain line patency by using dextrose or saline.
Treatment-emergent adverse events were assessed in a double-blind, multicenter clinical study comparing ibuprofen lysine to placebo therapy in 136 premature neonates within a 30 day follow up period. In the study, sinus tachycardia, heart failure, inguinal hernia, feeding problems, seizures, hypotension, and hyperglycemia were reported, although the association of these events with ibuprofen lysine is unknown. Ibuprofen's long term safety and effects on neurodevelopmental outcome, neurological disease, and growth, as well as disease processes associated with neonatal prematurity such as retinopathy of prematurity and chronic lung disease, have not been assessed.
Overall, adverse renal events were more common in the ibuprofen lysine treated group (14/68) when compared to the placebo treated group (10/68). The specific incidence of these events were reported as renal failure (unspecified) (1% vs. 3%), renal impairment or insufficiency (6% vs. 4%), reduction in renal output (3% vs. 1%), increase in blood creatinine (3% vs. 1%), hyperuricemia (7% vs. 4%), and hyperuricemia with hematuria (1% vs. 1%). Edema was reported in 4% of ibuprofen lysine treated neonates and in none of the placebo treated neonates. 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. The degree of ibuprofen induced decreases in renal perfusion may be inversely related to kidney maturity, which is a function of both birth age and gestational age. In other studies, adverse events classified as renal insufficiency including oliguria, elevated BUN, elevated creatinine, or renal failure were reported in ibuprofen treated infants. Ibuprofen lysine is contraindicated for use in preterm infants with significant impairment of renal function.
Intraventricular hemorrhage, a known sequelae of prematurity, was reported to occur in 20/68 (29.4%) of patients treated with ibuprofen lysine and in 16/68 (23.5%) of patients treated with placebo. No significant differences were noted in the incidence of grades 3 and 4 intraventricular hemorrhage between the ibuprofen lysine and placebo treated groups. Other bleeding events, unspecified, occurred less frequently in the ibuprofen lysine treated group 4/68 then in the placebo treated group 9/68. Ibuprofen induced changes in platelet aggregation may contribute to prolonged bleeding time, and this effect may be exaggerated in patients with an underlying hemostatic defect.
Gastrointestinal disorders such as non-necrotizing enterocolitis were reported in 15/68 (22%) of patients treated with ibuprofen lysine and in 12/68 of patients treated with placebo in a multicenter trial. No significant differences were noted in the incidence of stage 2 or 3 necrotizing enterocolitis between the ibuprofen lysine and placebo treated groups. Both necrotizing enterocolitis and gastrointestinal perforation have been reported during the postmarketing surveillance period. Two cases of spontaneous GI perforation (intestinal) without signs of necrotizing enterocolitis also occurred after treatment of PDA with oral ibuprofen in two patients (gestational ages 29 and 30 weeks). Abdominal distension, gastroesophageal reflux, gastritis, and ileus have been reported in patients treated with ibuprofen lysine; a causal relationship has not been established. Gastrointestinal events may be the result of prostaglandin synthesis suppression and bleeding time prolongation due to changes in platelet aggregation. Concomitant usage of anticoagulants or oral corticosteroids and duration of NSAID use are known to increase the risk of severe GI events in adults. Consider alternate therapies in patients with gastrointestinal abnormalities or GI perforation. Monitor for GI bleeding, as condition of neonate warrants. Abdominal distention and feeding problems have also been reported. Long-term safety and effects on growth have not been assessed.
Apnea occurred in 19/68 (28%) of ibuprofen lysine treated patients as compared with 18/68 of placebo treated patients. In the same trial, respiratory failure (10% vs. 4%) and atelectasis (4% vs. 1%) were reported more frequently with ibuprofen lysine treatment. A preterm neonate (gestational age 32 weeks) with respiratory distress syndrome developed pulmonary hypertension within 1 hour of the second dose of ibuprofen lysine for PDA closure. Severe hypoxemia was observed with upper-limb oxygen saturation below 70% during ventilation and a FiO2 of 1. Echocardiography showed closure of the ductus arteriosus and a significant right-to-left shunt through the foramen ovale with low right-ventricular output, tricuspid regurgitation, and an estimated peak pulmonary arterial pressure of about 50 mmHg. Inhaled nitric oxide therapy (up to 15 ppm) was started immediately and led to resolution of the hypoxemia within about 20 minutes; the FiO2 dropped from 1 to 0.35-0.40 within about 50 minutes. Resolution of pulmonary hypertension and closure of the ductus arteriosus were confirmed by echocardiography 8 hours after nitric oxide was started. The patient died of progressive worsening of clinical conditions attributed to generalized sepsis on day 5 of life. Postmortem findings were aspecific and compatible with immature lungs that had been ventilated since birth. Arterial vessels showed no thickening or intimal-medial alterations. In a group of 227 mechanically ventilated neonates, 3 with severe respiratory distress syndrome had moderate pulmonary hypertension that resolved after nitric oxide treatment. The neonates received ibuprofen lysine 10 mg/kg at a median age of 20 hours (range, 2-168 hours) and 5 mg/kg 24 and 48 hours after the first dose if there was no significant renal side effect, intraventricular hemorrhage, low platelet count, or coagulopathy. The long-term respiratory implications of ibuprofen lysine receipt, such as the incidence of chronic lung disease, are unexamined beyond the 36 weeks post-conceptual age observation period.
Dermatologic reactions, including skin ulcer and skin irritation, were reported in 16% of 68 patients treated with ibuprofen lysine and in 6% of 68 patients treated with placebo. Extravasation of ibuprofen lysine injection may lead to skin irritation or an injection site reaction. Drug reaction with eosinophilia and systemic symptoms (DRESS) was reported during postmarketing experience. NSAIDS, including ibuprofen, can cause serious skin reactions which can be fatal. Reported NSAID induced allergic reactions include anaphylactoid reactions such as anaphylactic shock, pruritus, rash, urticaria, exfoliative dermatitis, erythema nodosum, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis (AGEP). Discontinue ibuprofen at the first appearance of skin rash or any other sign of hypersensitivity.
NSAIDs have been associated with hepatotoxicity such as hepatitis or jaundice. In the multicenter study, jaundice and cholestasis were reported, although the association of the events with ibuprofen lysine is unknown. Monitor patients closely if elevated hepatic enzymes are observed during therapy. Ibuprofen lysine is known to displace bilirubin from albumin binding sites, hyperbilirubinemia may result.
Chronic adult use of ibuprofen has been shown to cause platelet dysfunction; this effect, however, is transient and reversible. Anemia has been reported in 22/68 (32%) of patients treated with ibuprofen lysine and in 17/68 of patients treated with placebo. Neutropenia and thrombocytopenia have been reported in patients treated with ibuprofen lysine; a causal relationship has not been established. Hematologic effects (< 1%) due to oral ibuprofen in other populations include neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia, pancytopenia, and thrombocytopenia.
The incidence of infections reported in 68 patients treated with ibuprofen lysine compared to 68 patients treated with placebo include sepsis (43% vs. 37%), respiratory infection (19% vs. 13%), and urinary tract infection (9% vs. 4%). Ibuprofen may mask the signs and symptoms of an infection.
Ibuprofen lysine is only indicated for use in premature neonates <= 32 weeks gestational age who weigh 500-1500 grams. This drug is not indicated for use in term neonates, older neonates, or infants.
Ibuprofen lysine, like other nonsteroidal anti-inflammatory agents, can inhibit platelet aggregation. This effect may be exaggerated in patients with underlying hemostatic defects. Use is contraindicated in patients with coagulopathy or thrombocytopenia and in patients who are actively bleeding, especially those with intracranial bleeding or GI bleeding. 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. Use with caution in patients expected to undergo surgery. Anemia may be exacerbated with the use of NSAIDs. This may be due to fluid retention, GI blood loss, or an incompletely described effect upon erythrogenesis. Follow hemoglobin values in at risk patients.
Ibuprofen lysine is contraindicated in patients 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 aortic coarctation). Typically, clinical trials involving ibuprofen lysine have excluded neonates with hypotension or hypertension. Conditions such as congestive heart failure or hypertension can be exacerbated with NSAID use.
Ibuprofen lysine is contraindicated in preterm neonates with an untreated suspected or proven infection. As NSAIDs may mask the signs of infection, neonates must be monitored closely during therapy. Caution should be exercised when this drug is used in patients with an active controlled infection or in neonates at risk of infection.
Ibuprofen lysine should be administered via intravenous infusion only; avoid subcutaneous administration and intramuscular administration. Administer carefully to prevent extravasation, as the solution may be irritating to tissue.
Due to the role of prostaglandins in renal function and hemodynamics, urine output should be closely monitored during therapy with ibuprofen lysine. Use is contraindicated in preterm neonates with severe renal impairment or renal failure. Use with caution in neonates with mild to moderate renal impairment; if anuria or marked oliguria (urinary output < 0.6 mL/kg/hour) is evident at the time of a scheduled dose of ibuprofen lysine, dosage should be held until laboratory studies indicate that renal function has returned to normal. The rate and extent of electrolyte and water elimination may be affected by NSAID induced changes in renal function. Correction of preexisting electrolyte imbalance and periodic determinations of serum electrolytes and renal function are prudent.
Ibuprofen lysine may alter mesenteric hemodynamics, use is therefore contraindicated in preterm neonates with, or who are suspected of having, necrotizing enterocolitis . A decrease in blood flow to the bowel in susceptible patients may result in intestinal tissue death and perforation. Patients with gastrointestinal malformations, GI perforation, or impaired intestinal circulation are not good candidates for pharmacologic closure of PDA. Severe gastrointestinal effects, due to alterations in prostaglandin synthesis and topical irritation, have been reported in adult patients treated with chronic oral NSAIDs; monitor for fecal occult blood as condition of neonate warrants.
Ibuprofen lysine has been shown to displace bilirubin from albumin binding-sites; therefore, use with caution in patients with elevated total bilirubin, as indicated by jaundice or laboratory result.
Because hepatotoxicities have been reported in adults treated chronically with oral NSAIDs such as ibuprofen lysine, and prospective studies of neonates with hepatic impairment have not been conducted, monitor for signs and symptoms of hepatic disease.
Ibuprofen lysine is indicated for use in premature neonates only; it should not be used during pregnancy.
Ibuprofen lysine is indicated for use in premature neonates only; do not use in breast-feeding women. Acetaminophen and ibuprofen, products intended for use in adult patients, are both considered to be usually compatible with breast-feeding by the American Academy of Pediatrics (AAP) and may be appropriate alternatives.
For treatment of a clinically significant patent ductus arteriosus (PDA) in premature infants when usual medical management such as fluid restriction, diuretics, and respiratory support is ineffective:
NOTE: Administration as a prophylactic is not recommended as a PDA may spontaneously close after birth.
NOTE: Although the clinical trial was conducted among infants with an asymptomatic PDA, reserve treatment for infants with a clinically significant PDA, as the long-term consequences of treatment have not been evaluated.
Intravenous dosage:
Premature neonates <= 32 weeks gestation who weigh 500-1500 g: Initially, 10 mg/kg IV followed, if necessary, by 2 doses of 5 mg/kg IV at 24-hour intervals. Base all doses on birth weight. Dose should be held in cases of oliguria (< 0.6 ml/kg/hour) or anuria. If the ductus arteriosus fails to close or reopens, a second course of ibuprofen lysine, alternative pharmacological therapy, or surgical closure may be necessary.
Maximum Dosage Limits:
-Adults
Safe and effective use has not been established.
-Elderly
Safe and effective use has not been established.
-Children
Safe and effective use has not been established.
-Infants
Safe and effective use has not been established.
-Neonates
Safe and effective use has not been established.
Premature neonates (<= 32 weeks gestation): 10 mg/kg/day IV.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Use is contraindicated in patients with significant renal impairment; specific guidelines for dosage adjustments in renal impairment are not available.
*non-FDA-approved indication
Acetaminophen; Ibuprofen: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Alprostadil: (Contraindicated) As ibuprofen lysine is used for the pharmacologic closure of patent ductus arteriosus (PDA), do not administer to patients who require alprostadil injection for dilation of the ductus arteriosus for oxygenation and perfusion. Alprostadil injection for pediatric use (Prostin VR) has been used with the standard therapy for neonates with restricted pulmonary or systemic blood flow which includes antibiotics (e.g., penicillin and gentamicin), vasopressors (e.g., dopamine, isoproterenol), cardiac glycosides, and diuretics (e.g., furosemide).
Amikacin: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Amiloride: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Aminoglycosides: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Amlodipine; Celecoxib: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Atenolol; Chlorthalidone: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Azilsartan; Chlorthalidone: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Bumetanide: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Bupivacaine; Meloxicam: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Celecoxib: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Celecoxib; Tramadol: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Chlorothiazide: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Chlorthalidone: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Diclofenac: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Diclofenac; Misoprostol: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Diflunisal: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Diphenhydramine; Ibuprofen: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Diphenhydramine; Naproxen: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Ethacrynic Acid: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Etodolac: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Fenoprofen: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Flurbiprofen: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Furosemide: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Gentamicin: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Hydrocodone; Ibuprofen: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Ibuprofen: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Ibuprofen; Famotidine: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Ibuprofen; Oxycodone: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Ibuprofen; Pseudoephedrine: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Indomethacin: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Ketoprofen: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Ketorolac: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Loop diuretics: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Meclofenamate Sodium: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Mefenamic Acid: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Meloxicam: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Metolazone: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Nabumetone: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Naproxen: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Naproxen; Esomeprazole: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Naproxen; Pseudoephedrine: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Nonsteroidal antiinflammatory drugs: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Oxaprozin: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Paromomycin: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Piroxicam: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Plazomicin: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Potassium-sparing diuretics: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Spironolactone: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Streptomycin: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Sulindac: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Sumatriptan; Naproxen: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Thiazide diuretics: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Tobramycin: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
Tolmetin: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs, including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects, may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID should be avoided.
Torsemide: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Triamterene: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
The exact mechanism by which ibuprofen lysine causes closure of a patent ductus arteriosus (PDA) in neonates is not known. However, it is thought that the inhibition of prostaglandin synthesis is relevant. Local release of prostaglandins results in the dilation of, and may delay the closure of, the ductus. Ibuprofen blocks arachidonate binding resulting in competitive inhibition of both cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, which in turn limits the COX-1 and COX-2 catalyzed conversion of arachidonic acid to prostaglandin G2 (PGG2) and subsequent prostaglandin and thromboxane synthesis. Based on in vitro information, ibuprofen has about equal inhibitory effects on COX-1 and COX-2.
Ibuprofen lysine is administered as an intravenous infusion. Pharmacokinetic data were obtained from 54 premature infants included in a double-blind, placebo-controlled, randomized, multicenter study. The infants were less than 30 weeks gestational age, weighed 500-1000 g, and exhibited asymptomatic PDA with echocardiographic documentation of ductal shunting. The study measured the average clearance and volume of distribution values of racemic ibuprofen at birth to be 3 mL/kg/hour and 320 mL/kg, respectively. Clearance increased rapidly with postnatal age (an average increase of approximately 0.5 mL/kg/hour per day). Inter-individual variability in clearance and volume of distribution were 55% and 14%, respectively. In general, the half-life in infants is estimated to be more than 10 times longer than in adults. Metabolism and excretion in premature infants have not been studied. In adults, ibuprofen is metabolized via hepatic oxidation by cytochrome P450 2C9 to two inactive metabolites then excreted in the urine; 50-60% as metabolites and approximately 10% as unchanged drug. Some biliary excretion may occur. Renal function and the enzymes associated with drug metabolism, in general, are underdeveloped at birth and substantially increase in the days after birth.
Affected cytochrome P450 isoenzymes: CYP2C9
-Special Populations
Hepatic Impairment
No pharmacokinetic data are available for ibuprofen lysine in neonates with hepatic impairment.
Renal Impairment
No pharmacokinetic data are available for ibuprofen lysine in neonates with renal impairment.
Pediatrics
Ibuprofen lysine pharmacokinetic data were obtained from 54 premature infants included in a double-blind, placebo-controlled, randomized, multicenter study. The infants were less than 30 weeks gestational age, weighed 500-1000 g, and exhibited asymptomatic PDA with echocardiographic documentation of ductal shunting. The study measured the average clearance and volume of distribution values of racemic ibuprofen at birth to be 3 mL/kg/hour and 320 mL/kg, respectively. Clearance increased rapidly with postnatal age (an average increase of approximately 0.5 mL/kg/hour per day). Inter-individual variability in clearance and volume of distribution were 55% and 14%, respectively. In general, the half-life of ibuprofen in infants is estimated to be more than 10 times longer than in adults. The metabolism and excretion of ibuprofen lysine in premature infants have not been studied. No pharmacokinetic data are available in neonates with either renal or hepatic impairment.