Infants' Ibuprofen (ibuprofen)

To minimize the potential risk of adverse cardiovascular and/or GI events, use the lowest possible effective dosage and shortest duration of therapy consistent with treatment goals of the patient. Dosage of ibuprofen must be carefully adjusted according to individual requirements and response, using the lowest possible effective dosage.

Dosage of ibuprofen lysine is expressed in terms of ibuprofen.

Ibuprofen is administered orally or IV. Ibuprofen lysine is administered IV.

Ibuprofen is also commercially available in the following fixed-combination tablets for oral use: ibuprofen and famotidine (Duexis(R)); ibuprofen and hydrocodone bitartrate. See the full prescribing information for administration of each of these combination products.

Ibuprofen is also commercially available in various over-the-counter (OTC) preparations as a single ingredient or in combination with other analgesics (e.g., acetaminophen), antihistamines, or decongestants. See the FDA Orange Book and the manufacturer's Drug Facts for further information.

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Ibuprofen is metabolized mainly via cytochrome P-450 (CYP) isoenzyme 2C9-mediated hydroxylation of R- and S-ibuprofen. There is no evidence of enzyme induction.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Ibuprofen is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis, serious dermatologic reactions) to the drug or any ingredient in the formulation.

*Nonsteroidal anti-inflammatory agents (NSAIAs) generally are contraindicated in patients in whom asthma, urticaria, or other sensitivity reactions are precipitated by aspirin or other NSAIAs, since there is potential for cross-sensitivity between NSAIAs and aspirin, and severe, potentially fatal, bronchospasm can occur in such patients.

*NSAIAs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Contraindications with IV Ibuprofen Lysine for PDA

*Neonates with proven or suspected untreated infection.

*Neonates with active bleeding, such as those with intracranial hemorrhage or GI bleeding, and in neonates with thrombocytopenia or underlying coagulation defect.

*Neonates with suspected necrotizing enterocolitis.

*Neonates with substantially impaired renal function.

*Neonates with congenital heart disease when patency of the ductus arteriosus is necessary for adequate pulmonary or systemic blood flow (e.g., neonates with pulmonary atresia, severe tetralogy of Fallot, or severe coarctation of the aorta).

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects reported in at least 5% of adults receiving IV ibuprofen include nausea, flatulence, vomiting, headache, hemorrhage, and dizziness.

Adverse effects reported in at least 2% of pediatric patients receiving IV ibuprofen include infusion site pain, vomiting, nausea, anemia, and headache.

The most common type of adverse effect occurring with ibuprofen tablets is GI, and was reported in 4-16% of patients in clinical studies.

Adverse effects occurring in 1-10% of patients receiving ibuprofen oral suspension include abnormal renal function, anemia, dizziness, edema, elevated transaminases, fluid retention, GI effects (e.g., abdominal pain, bloating, constipation, diarrhea, dyspepsia, epigastric pain, flatulence, heartburn, nausea, vomiting), headaches, increased bleeding times, nervousness, pruritis, rashes (including maculopapular), and tinnitus.

Adverse effects occurring in at least 10% of premature infants receiving IV ibuprofen lysine for the treatment of patent ductus arteriosus (PDA) include sepsis, anemia, intraventricular bleeding, apnea, GI disorders, impaired renal function, respiratory infection, skin lesions, hypoglycemia, hypocalcemia, and respiratory failure.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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The manufacturers state that the safety and efficacy of oral ibuprofen in children <6 months of age have not been established.

Pediatric patients receiving ibuprofen dosages exceeding 30 mg/kg daily and those who have had abnormal liver function test results associated with prior NSAIA therapy should be carefully monitored for signs and symptoms of early liver dysfunction.

Safety and efficacy of IV ibuprofen have been established for treatment of pain and fever in pediatric patients 3 months of age and older. Use of IV ibuprofen for these indications is supported by evidence from one open-label and acetaminophen-controlled study of fever, as well as additional safety data from four studies in 164 pediatric patients, supportive pediatric data from other approved ibuprofen preparations, and evidence from adequate and well-controlled studies in adults. The most common adverse effects of IV ibuprofen in pediatric patients are infusion site pain, vomiting, nausea, anemia, and headache. Efficacy of IV ibuprofen for relief of pain or reduction of fever has not been established in pediatric patients <3 months of age.

Long-term follow-up (beyond a postconceptional age of 36 weeks) of premature neonates receiving ibuprofen lysine for patent ductus arteriosus (PDA) has not been conducted. The effects of ibuprofen on neurodevelopmental outcome, growth, and other complications of prematurity (e.g., retinopathy of prematurity, chronic lung disease) have not been assessed.

Safety and efficacy of ibuprofen lysine have been established only in premature infants.

Use of NSAIAs during pregnancy at about 30 weeks' gestation or later can cause premature closure of the fetal ductus arteriosus, and use at about 20 weeks' gestation or later has been associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, use of NSAIAs should be avoided in pregnant women at about 30 weeks' gestation or later; if NSAIA therapy is necessary between about 20 and 30 weeks' gestation, the lowest effective dosage and shortest possible duration of treatment should be used. Monitoring of amniotic fluid volume via ultrasound examination should be considered if the duration of NSAIA treatment exceeds 48 hours; if oligohydramnios occurs, the drug should be discontinued and follow-up instituted according to clinical practice. Pregnant women should be advised to avoid use of NSAIAs beginning at 20 weeks' gestation unless otherwise advised by a clinician; they also should be informed that NSAIAs should be avoided beginning at 30 weeks' gestation because of the risk of premature closure of the fetal ductus arteriosus and that monitoring for oligohydramnios may be necessary if NSAIA therapy is required for longer than 48 hours' duration between about 20 and 30 weeks of gestation.

Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment has been observed, on average, following days to weeks of maternal NSAIA use, although oligohydramnios has been observed infrequently as early as 48 hours after initiation of NSAIA therapy. Oligohydramnios is often, but not always, reversible following discontinuance of NSAIA therapy. Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation. A limited number of case reports have described maternal NSAIA use and neonatal renal dysfunction, in some cases irreversible, without oligohydramnios. Some cases of neonatal renal dysfunction have required treatment with invasive procedures such as exchange transfusion or dialysis. Methodologic limitations of these postmarketing studies and case reports include lack of a control group; limited information regarding dosage, duration, and timing of drug exposure; and concomitant use of other drugs. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAIA use. Available data on neonatal outcomes generally involved preterm infants, and the extent to which certain reported risks can be generalized to full-term infants is uncertain.

Animal data indicate that prostaglandins have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, inhibitors of prostaglandin synthesis, such as ibuprofen, were associated with increased preimplantation and postimplantation losses. Prostaglandins also have an important role in fetal kidney development. In animal studies, inhibitors of prostaglandin synthesis impaired kidney development at clinically relevant doses.

There are no adequate and well-controlled studies of ibuprofen in pregnant women. In animal reproduction studies, no clear developmental effects were observed in rabbits or rats given ibuprofen throughout the gestational period at dosages up to 0.4 or 0.5 times, respectively, the maximum recommended human dosage (MRHD). An increase in membranous ventricular septal defects was reported in rats given ibuprofen on gestation days 9 and 10 at a dosage of 0.8 times the MRHD.

The effects of ibuprofen on labor and delivery are unknown. In studies in rats, drugs that inhibit prostaglandin synthesis, including NSAIAs, delayed parturition and increased the incidence of stillbirth.

Limited data indicate that ibuprofen is distributed into milk, resulting in infant exposures of 0.06-0.6% of the maternal weight-adjusted daily dosage. Adverse effects on breast-fed infants or effects on milk production have not been reported to date. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for ibuprofen and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

The manufacturers make no specific dosage recommendations in geriatric patients; however, geriatric patients are generally at a greater risk for NSAIA-associated serious cardiovascular, GI, and/or renal adverse effects. If the expected benefits outweigh the potential risks of therapy, initiate at the lower end of the dosage range and monitor for adverse effects.

Geriatric patients are at increased risk for NSAIA-associated serious adverse cardiovascular, GI, and renal effects. Many of the spontaneous reports of fatal adverse GI effects in patients receiving NSAIAs involve geriatric individuals. If the anticipated benefits of ibuprofen therapy outweigh the potential risks, ibuprofen should be initiated at the lower end of the dosing range and patients should be monitored for adverse effects.

Clinical studies of IV ibuprofen did not include sufficient numbers of patients >=65 years of age to determine whether geriatric patients respond differently than younger adults. Dosage should be selected with caution, starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, and/or cardiac function and concomitant disease and drug therapy observed in the elderly.