Pharmacodynamics -

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that possesses anti-inflammatory, analgesic and antipyretic activity. Its mode of action, like that of other NSAIDs, is not completely understood, but may be related to prostaglandin synthetase inhibition. After absorption of the racemic ibuprofen, the [-]R-enantiomer undergoes interconversion to the [+]S-form. The biological activities of ibuprofen are associated with the [+]S-enantiomer.

Pharmacokinetics -

Ibuprofen is a racemic mixture of [-]R- and [+]S-isomers. In vivoand in vitro studies indicate that the [+]S-isomer is responsible for clinical activity. The [-]R-form, while thought to be pharmacologically inactive, is slowly and incompletely (~60%) interconverted into the active [+]S species in adults. The degree of interconversion in children is unknown, but is thought to be similar. The [-]R-isomer serves as a circulating reservoir to maintain levels of active drug. Ibuprofen is well absorbed orally, with less than 1% being excreted in the urine unchanged. It has a biphasic elimination time curve with a plasma half-life of approximately 2 hours. Studies in febrile children have established the dose-proportionality of 5 and 10 mg/kg doses of ibuprofen. Studies in adults have established the dose-proportionality of ibuprofen as a single oral dose from 50 to 600 mg for total drug and up to 1200 mg for free drug.

Absorption -

In vivo studies indicate that ibuprofen is well absorbed orally from the suspension formulation, with peak plasma levels usually occurring within 1 to 2 hours (see Table 1).

Table 1

Pharmacokinetic Parameters of Ibuprofen Oral Suspension [Mean values (% coefficient of variation)]

Legend:AUC inf= Area-under-the-curve to infinity

T max= Time-to-peak plasma concentration

C max= Peak plasma concentration

Cl/F = Clearance divided by fraction at drug absorbed

Antacids -

A bioavailability study in adults has shown that there was no interference with the absorption of ibuprofen when given in conjunction with an antacid containing both aluminum hydroxide and magnesium hydroxide.

H-2 Antagonists -

In studies with human volunteers, coadministration of cimetidine or ranitidine with ibuprofen had no substantive effect on ibuprofen serum concentrations.

Food Effects -

Absorption is most rapid when ibuprofen is given under fasting conditions. Administration of ibuprofen oral suspension with food affects the rate but not the extent of absorption. When taken with food, T maxis delayed by approximately 30 to 60 minutes, and peak levels are reduced by approximately 30 to 50%.

Distribution -

Ibuprofen, like most drugs of its class, is highly protein bound (>99% bound at 20 μg/mL). Protein binding is saturable and at concentrations >20 μg/mL binding is non-linear. Based on oral dosing data there is an age- or fever-related change in volume of distribution for ibuprofen. Febrile children <11 years old have a volume of approximately 0.2 L/kg while adults have a volume of approximately 0.12 L/kg. The clinical significance of these findings is unknown.

Metabolism -

Following oral administration, the majority of the dose was recovered in the urine within 24 hours as the hydroxy-(25%) and carboxypropyl-(37%) phenylpropionic acid metabolites. The percentages of free and conjugated ibuprofen found in the urine were approximately 1% and 14%, respectively. The remainder of the drug was found in the stool as both metabolites and unabsorbed drug.

Elimination -

Ibuprofen is rapidly metabolized and eliminated in the urine. The excretion of ibuprofen is virtually complete 24 hours after the last dose. It has a biphasic plasma elimination time curve with a half-life of approximately 2.0 hours. There is no difference in the observed terminal elimination rate or half-life between children and adults, however, there is an age- or fever-related change in total clearance. This suggests that the observed change in clearance is due to changes in the volume of distribution of ibuprofen (see Table 1 for Cl/F values).

Clinical Studies -

Controlled clinical trials comparing doses of 5 and 10 mg/kg ibuprofen oral suspension and 10-15 mg/kg of acetaminophen elixir have been conducted in children 6 months to 12 years of age with fever primarily due to viral illnesses. In these studies there were no differences between treatments in fever reduction for the first hour and maximum fever reduction occurred between 2 and 4 hours. Response after 1 hour was dependent on both the level of temperature elevation as well as the treatment. In children with baseline temperatures at or below 102.5ºF both ibuprofen doses and acetaminophen were equally effective in their maximum effect. In children with temperatures above 102.5ºF, the ibuprofen 10 mg/kg dose was more effective. By 6 hours, children treated with ibuprofen 5 mg/kg tended to have recurrence of fever, whereas children treated with ibuprofen 10 mg/kg still had significant fever reduction at 8 hours. In control groups treated with 10 mg/kg acetaminophen, fever reduction resembled that seen in children treated with 5 mg/kg of ibuprofen, with the exception that temperature elevation tended to return 1-2 hours earlier.

In patients with primary dysmenorrhea, ibuprofen has been shown to reduce elevated levels of prostaglandin activity in the menstrual fluid and to reduce testing and active intrauterine pressure, as well as the frequency of uterine contractions. The probable mechanism of action is to inhibit prostaglandin synthesis rather than simply to provide analgesia.

Pharmacodynamics

In a healthy volunteer study, ibuprofen 400 mg given once daily, administered 2 hours prior to immediate-release aspirin (81 mg) for 6 days, showed an interaction with the antiplatelet activity of aspirin as measured by % serum thromboxane B2 (TxB2) inhibition at 24 hours following the day-6 aspirin dose [53%]. An interaction was still observed, but minimized, when ibuprofen 400 mg given once-daily was administered as early as 8 hours prior to the immediate-release aspirin dose [90.7%]. However, there was no interaction with the antiplatelet activity of aspirin when ibuprofen 400 mg, given once daily, was administered 2 hours after (but not concomitantly, 15 min, or 30 min after) the immediate-release aspirin dose [99.2%].

In another study, where immediate-release aspirin 81 mg was administered once daily with ibuprofen 400 mg given three times daily (1, 7, and 13 hours post-aspirin dose) for 10 consecutive days, the mean % serum thromboxane B2 (TxB2) inhibition suggested no interaction with the antiplatelet activity of aspirin [98.3%]. However, there were individual subjects with serum TxB2 inhibition below 95%, with the lowest being 90.2%.

When a similarly designed study was conducted with enteric-coated aspirin, where healthy subjects were administered enteric-coated aspirin 81 mg once daily for 6 days and ibuprofen 400 mg three times daily (2, 7 and 12 h post-aspirin dose) for 6 days, there was an interaction with the antiplatelet activity at 24 hours following the day-6 aspirin dose [67%]. [ See Precautions/Drug Interactions].

Cardiovascular Thrombotic Events

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.

To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as ibuprofen, increases the risk of serious gastrointestinal (GI) events (see WARNINGS).

Status Post Coronary Artery Bypass Graft (CABG) Surgery

Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG (see CONTRAINDICATIONS).

Post-MI Patients

Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.

Avoid the use of Ibuprofen Oral Suspension in patients with a recent MI unless the benefits are expected to outweigh the risks of recurrent CV thrombotic events. If Ibuprofen Oral Suspension is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

Hypertension

NSAIDs, including Ibuprofen Oral Suspension, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Ibuprofen Oral Suspension, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

Heart Failure and Edema

The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of ibuprofen may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)] (see Drug Interactions).

Avoid the use of Ibuprofen Oral Suspension in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Ibuprofen Oral Suspension is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation

NSAIDs, including Ibuprofen Oral Suspension, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.

NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleedingwho use NSAIDs have a greater than 10-fold risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.

To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

Renal Effects

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly.

Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

Advanced Renal Disease

No information is available from controlled clinical studies regarding the use of Ibuprofen Oral Suspension in patients with advanced renal disease. Therefore, treatment with Ibuprofen Oral Suspension is not recommended in these patients with advanced renal disease. If Ibuprofen Oral Suspension therapy must be initiated, close monitoring of the patient’s renal function is advisable.

Anaphylactoid Reactions

As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to Ibuprofen Oral Suspension. Ibuprofen Oral Suspension should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONSand PRECAUTIONS – Preexisting Asthma). Emergency help should be sought in cases where an anaphylactoid reaction occurs.

Serious Skin Reactions

NSAIDs, including Ibuprofen Oral Suspension, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. NSAIDs can also cause fixed drug eruption (FDE). FDE may present as a more severe variant known as generalized bullous fixed drug eruption (GBFDE), which can be life-threatening. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of Ibuprofen Oral Suspension at the first appearance of skin rash or any other sign of hypersensitivity. Ibuprofen Oral Suspension is contraindicated in patients with previous serious skin reactions to NSAIDs (see CONTRAINDICATIONS).

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as Ibuprofen Oral Suspension. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue Ibuprofen Oral Suspension and evaluate the patient immediately.

Fetal Toxicity

Premature Closure of Fetal Ductus Arteriosus:

Avoid use of NSAIDs, including Ibuprofen Oral Suspension, in pregnant women at about 30 weeks gestation and later. NSAIDs including Ibuprofen Oral Suspension, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.

Oligohydramnios/Neonatal Renal Impairment:

Use of NSAIDs, including Ibuprofen Oral Suspension, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.

If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit Ibuprofen Oral Suspension use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if Ibuprofen Oral Suspension treatment extends beyond 48 hours. Discontinue Ibuprofen Oral Suspension if oligohydramnios occurs and follow up according to clinical practice [ see PRECAUTIONS; Pregnancy].

General

Ibuprofen Oral Suspension cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

The pharmacological activity of Ibuprofen Oral Suspension in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Hepatic Effects

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Ibuprofen Oral Suspension. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with Ibuprofen Oral Suspension. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), Ibuprofen Oral Suspension should be discontinued.

Hematological Effects

Anemia is sometimes seen in patients receiving NSAIDs, including Ibuprofen Oral Suspension. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including Ibuprofen Oral Suspension, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

In two postmarketing clinical studies the incidence of a decreased hemoglobin level was greater than previously reported. Decrease in hemoglobin of 1 gram or more was observed in 17.1% of 193 patients on 1600 mg ibuprofen daily (osteoarthritis), and in 22.8% of 189 patients taking 2400 mg of ibuprofen daily (rheumatoid arthritis). Positive stool occult blood tests and elevated serum creatinine levels were also observed in these studies.

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving Ibuprofen Oral Suspension who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.

Preexisting Asthma

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, Ibuprofen Oral Suspension should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Aseptic Meningitis

Aseptic meningitis, with fever and coma, has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease.

Diabetics

Ibuprofen Oral Suspension contains 270 mg high fructose corn syrup and 0.83 calories per mL, or 1350 mg high fructose corn syrup and 4.15 calories per teaspoonful, which should be taken into consideration when treating diabetic patients with this product.

Information for Patients:

Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

1. Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately (see WARNINGS).
2. Ibuprofen Oral Suspension, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization or even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS - Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation).
3. Serious Skin Reactions, including DRESS
   Advise patients to stop taking Ibuprofen Oral Suspension immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible (see WARNINGS).
4. Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur (see WARNINGS).
5. Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritis, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
6. Patients should be informed of the signs of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS).
7. Fetal Toxicity
   Inform pregnant women to avoid use of Ibuprofen Oral Suspension and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with Ibuprofen Oral Suspension is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours (see WARNINGS; Fetal Toxicity, PRECAUTIONS; Pregnancy).

Laboratory Tests

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, Ibuprofen Oral Suspension should be discontinued.

Drug Interactions

Pregnancy

Risk Summary

Use of NSAIDs, including Ibuprofen Oral Suspension, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of Ibuprofen Oral Suspension use between about 20 and 30 weeks of gestation, and avoid Ibuprofen Oral Suspension use at about 30 weeks of gestation and later in pregnancy [see WARNINGS; Fetal Toxicity].

Premature Closure of Fetal Ductus Arteriosus

Use of NSAIDs, including Ibuprofen Oral Suspension, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.

Oligohydramnios/Neonatal Renal Impairment

Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment.

Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. Animal reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. However, animal reproduction studies are not always predictive of human response. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as ibuprofen, resulted in increased pre- and post-implantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses.

The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Premature Closure of Fetal Ductus Arteriosus:

Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including Ibuprofen Oral Suspension, can cause premature closure of the fetal ductus arteriosus (see WARNINGS; Fetal Toxicity).

Oligohydramnios/Neonatal Renal Impairment

If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If Ibuprofen Oral Suspension treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue Ibuprofen Oral Suspension and follow up according to clinical practice (see WARNINGS; Fetal Toxicity).

Data

Human Data

There are no adequate, well-controlled studies in pregnant women. Ibuprofen should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Premature Closure of Fetal Ductus Arteriosus:

Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus.

Oligohydramnios/Neonatal Renal Impairment:

Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis.

Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use.

Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain.

Labor and Delivery

In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of ibuprofen suspension on labor and delivery in pregnant women are unknown. Therefore, administration of Ibuprofen Oral Suspension is not recommended during labor and delivery.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Ibuprofen Oral Suspension, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of ibuprofen oral suspension in pediatric patients below the age of 6 months have not been established (see CLINICAL PHARMACOLOGY - Clinical Studies). Dosing of Ibuprofen Oral Suspension in children 6 months or older should be guided by their body weight (see DOSAGE AND ADMINISTRATION).

Geriatric Use

As with any NSAID, caution should be exercised in treating the elderly (65 years and older).

PEDIATRIC PATIENTS

ADULTS

Shake well before using.
Store at 20ºC to 25ºC (68ºF to 77ºF) [see USP Controlled Room Temperature].
Do not freeze.
Preserve in well-closed containers.

Manufactured by:
Kesin Pharma
Oldsmar, FL 34677
Rev. 01
Revised 11/2024