Brand names: Advil, Caldolor, IBU, Motrin, NeoProfen
Drug class: Reversible COX-1/COX-2 Inhibitors

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Prototypical NSAIA; propionic acid derivative.

Uses for Ibuprofen

When used for inflammatory diseases, pain, dysmenorrhea, or fever, consider potential benefits and risks of ibuprofen therapy as well as alternative therapies before initiating therapy with the drug. Use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.

Inflammatory Diseases

Symptomatic treatment of osteoarthritis and rheumatoid arthritis.

May be used in fixed combination with famotidine for symptomatic treatment of rheumatoid arthritis and osteoarthritis when use of famotidine to reduce the risk of upper GI ulcers is appropriate. Efficacy of the fixed combination in reducing the risk of gastric and/or duodenal ulcers was demonstrated in studies of 6 months’ duration in patients without a history of GI ulcer who generally were <65 years of age.

Management of juvenile rheumatoid arthritis in children.

Pericarditis

Reduction of pain, fever, and inflammation of pericarditis^{† [off-label]}; however, in the treatment of post-MI pericarditis, NSAIAs are potentially harmful and aspirin is the treatment of choice. (See Cardiovascular Thrombotic Effects under Cautions.)

Pain

Oral ibuprofen used for relief of mild to moderate pain; IV ibuprofen used for relief of mild to moderate pain and, in conjunction with opiates, for relief of moderate to severe pain.

NSAIAs considered first-line agents for mild to moderate migraine attacks or for severe attacks that have responded in the past to NSAIAs or nonopiate analgesics.

Self-medication for the temporary relief of minor aches and pain associated with the common cold, influenza, or sore throat; headache (including migraine); toothache; muscular aches; backache; minor pain of arthritis.

Used in fixed combination with hydrocodone for short-term treatment of acute pain that is severe enough to require an opiate analgesic and for which alternative treatments are inadequate.

Dysmenorrhea

Symptomatic management of primary dysmenorrhea.

Self-medication for the temporary relief of minor aches and pain associated with menstrual cramps.

Fever

Reduction of fever.

Self-medication for reduction of fever.

Patent Ductus Arteriosus (PDA)

Treatment of PDA in premature neonates (designated an orphan drug by FDA for this use). Used to promote closure of a clinically important PDA in premature neonates weighing 500–1500 g who are ≤32 weeks' gestational age when usual medical management (e.g., fluid restriction, diuretics, respiratory support) is ineffective. Limited follow-up data available; reserve for neonates with clinically important PDA.

Ibuprofen Dosage and Administration

General

• For inflammatory diseases, pain, dysmenorrhea, or fever, consider potential benefits and risks of ibuprofen therapy as well as alternative therapies before initiating therapy with the drug.

Administration

Ibuprofen: Administer orally (for inflammatory diseases, pain, dysmenorrhea, or fever) or by IV infusion (for pain or fever).

Ibuprofen lysine: Administer by IV infusion (for PDA).

Oral Administration

If GI disturbances occur, administer with meals or milk.

Fixed combination of ibuprofen and famotidine: Swallow tablets whole; do not chew, divide, crush, or cut tablets to provide a lower dose.

Pediatric Administration

Ibuprofen oral drops generally used in infants 6–23 months of age. Use the calibrated dosing device provided by the manufacturer for measurement of the dose.

Pediatric oral suspension and 100-mg chewable tablets commonly used in children 2–11 years of age. Use the calibrated dosage cup provided by the manufacturer for measurement of the dose of the suspension.

The 100-mg film-coated tablets may be used in children 6–11 years of age.

IV Administration (Ibuprofen)

Ensure patient is well hydrated.

Injection concentrate (100 mg/mL) must be diluted prior to IV administration. IV administration of the undiluted concentrate can cause hemolysis.

Use the commercially available ibuprofen 4-mg/mL (800 mg in 200 mL) premixed injection to administer 800-mg doses only.

Dilution

Dilute ibuprofen injection concentrate with an appropriate volume of 0.9% sodium chloride injection, 5% dextrose injection, or lactated Ringer’s injection to provide a solution containing ≤4 mg/mL.

Rate of Administration

Adults: Administer dose over ≥30 minutes.

Pediatric patients 6 months to 17 years of age: Administer dose over ≥10 minutes.

IV Administration (Ibuprofen Lysine)

Administer by IV infusion using IV port nearest to the IV insertion site.

Do not infuse simultaneously through same line as parenteral nutrition solutions. If same line must be used, interrupt infusion of the nutrition solution for 15 minutes before and after administration of ibuprofen; maintain line patency by infusing dextrose injection or sodium chloride injection.

Avoid extravasation (irritating to extravascular tissues).

Dilution

Dilute ibuprofen lysine injection with an appropriate volume of dextrose injection or sodium chloride injection.

Administer within 30 minutes of preparation; discard any unused solution.

Rate of Administration

Administer dose over 15 minutes.

Dosage

Dosage of ibuprofen lysine expressed in terms of ibuprofen.

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals. Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.

Pediatric Patients

Dosage in children should be guided by body weight.

Inflammatory Diseases

Juvenile Rheumatoid Arthritis

Oral

30–40 mg/kg daily divided into 3 or 4 doses. 20 mg/kg daily in divided doses may be adequate for children with mild disease.

Once clinical effect obtained, reduce dosage to lowest level that maintains adequate symptomatic control.

If dosage >30 mg/kg daily, carefully monitor for signs and symptoms of early liver dysfunction.

Pain

Oral

For mild to moderate pain in children 6 months to 2 years of age, 10 mg/kg every 6–8 hours; avoid disrupting the child's sleep pattern. (See Pediatric Use under Cautions.)

See Table 1 for recommended analgesic dosages for self-medication in children 6 months to 11 years of age.

Dose may be administered every 6–8 hours.

For self-medication of minor aches and pain in adolescents ≥12 years of age, 200 mg every 4–6 hours; may increase dosage to 400 mg every 4–6 hours (maximum 1.2 g daily) if needed.

In fixed combination with acetaminophen for self-medication of minor aches and pain in adolescents ≥12 years of age, 250 mg of ibuprofen every 8 hours.

IV

For children 6 months to <12 years of age, 10 mg/kg (up to 400 mg) every 4–6 hours as needed; do not exceed 40 mg/kg or 2.4 g (whichever is less) per 24-hour period.

For adolescents 12–17 years of age, 400 mg every 4–6 hours as needed (maximum 2.4 g per 24-hour period).

Fever

Oral

For children 6 months to 2 years of age: 5 mg/kg for temperatures <39°C; 10 mg/kg for temperatures ≥39°C. (See Pediatric Use under Cautions.)

See Table 2 for recommended antipyretic dosages for self-medication in children 6 months to 11 years of age.

Dose may be administered every 6–8 hours.

For self-medication of fever in adolescents ≥12 years of age, 200 mg every 4–6 hours; may increase dosage to 400 mg every 4–6 hours (maximum 1.2 g daily) if needed.

IV

For children 6 months to <12 years of age, 10 mg/kg (up to 400 mg) every 4–6 hours as needed; do not exceed 40 mg/kg or 2.4 g (whichever is less) per 24-hour period.

For adolescents 12–17 years of age, 400 mg every 4–6 hours as needed (maximum 2.4 g per 24-hour period).

Dysmenorrhea

Oral

For self-medication in adolescents 12–17 years of age, 200 mg every 4–6 hours; may increase to 400 mg every 4–6 hours (maximum 1.2 g daily) if necessary.

PDA

IV

Each course of therapy consists of 3 doses of ibuprofen lysine administered at 24-hour intervals.

Base dosage on neonate’s birth weight.

First dose is 10 mg/kg; second and third doses are 5 mg/kg each.

If anuria or oliguria (urine output <0.6 mL/kg per hour) is present at the time of a second or third dose, withhold the dose until laboratory determinations indicate that renal function has returned to normal.

If ductus arteriosus closes or is substantially constricted after completion of the first course, no further doses are necessary.

If ductus arteriosus fails to close or reopens, a second course of ibuprofen, alternative pharmacologic therapy, or surgery may be needed.

Adults

Inflammatory Diseases

Osteoarthritis or Rheumatoid Arthritis

Oral

1.2–3.2 g daily, given as 300 mg 4 times daily, or 400, 600, or 800 mg 3 or 4 times daily.

In fixed combination with famotidine, 800 mg of ibuprofen 3 times daily.

Pain

Oral

For mild to moderate pain, 400 mg every 4–6 hours as needed.

In fixed combination with hydrocodone, 200 mg of ibuprofen every 4–6 hours (maximum 1 g daily) as needed.

For self-medication of minor aches and pain, 200 mg every 4–6 hours; may increase dosage to 400 mg every 4–6 hours (maximum 1.2 g daily) if needed.

In fixed combination with acetaminophen for self-medication of minor aches and pain, 250 mg of ibuprofen every 8 hours.

For self-medication of migraine pain, 400 mg once in a 24-hour period.

IV

400–800 mg every 6 hours as needed.

Dysmenorrhea

Oral

400 mg every 4 hours as necessary; initiate at earliest onset of pain.

For self-medication, 200 mg every 4–6 hours; may increase to 400 mg every 4–6 hours (maximum 1.2 g daily) if necessary.

Fever

Oral

For self-medication, 200 mg every 4–6 hours; may increase to 400 mg every 4–6 hours (maximum 1.2 g daily) if needed.

IV

400 mg initially; then 400 mg every 4–6 hours or 100–200 mg every 4 hours.

Prescribing Limits

Pediatric Patients

Inflammatory Diseases

Juvenile Rheumatoid Arthritis

Oral

Maximum 50 mg/kg daily.

Pain

Oral

For mild to moderate pain in children 6 months to 2 years of age, maximum 40 mg/kg daily.

For self-medication of minor aches and pain in children 6 months to 11 years of age, do not exceed recommended dosage; do not administer recommended dose more than 4 times daily. (See Pediatric Use under Cautions.) Self-medication should not exceed 3 days unless otherwise directed by a clinician.

For self-medication of minor aches and pain in adolescents ≥12 years of age, maximum 1.2 g daily. Self-medication should not exceed 10 days unless otherwise directed by a clinician.

In fixed combination with acetaminophen for self-medication of minor aches and pains in adolescents ≥12 years of age, maximum 250 mg of ibuprofen every 8 hours. Self-medication should not exceed 10 days unless otherwise directed by a clinician.

IV

For children 6 months to <12 years of age, maximum 40 mg/kg or 2.4 g (whichever is less) per 24-hour period.

For adolescents 12–17 years of age, maximum 2.4 g per 24-hour period.

Fever

Oral

Maximum 40 mg/kg daily in children 6 months to 2 years of age.

For self-medication in children 6 months to 11 years of age, do not exceed recommended dosage; do not administer recommended dose more than 4 times daily. (See Pediatric Use under Cautions.) Self-medication should not exceed 3 days unless otherwise directed by a clinician.

For self-medication in adolescents ≥12 years of age, maximum 1.2 g daily. Self-medication should not exceed 3 days unless otherwise directed by a clinician.

IV

For children 6 months to <12 years of age, maximum 40 mg/kg or 2.4 g (whichever is less) per 24-hour period.

For adolescents 12–17 years of age, maximum 2.4 g per 24-hour period.

Dysmenorrhea

Oral

For self-medication in adolescents 12–17 years of age, maximum 1.2 g daily.

Adults

Inflammatory Diseases

Osteoarthritis or Rheumatoid Arthritis

Oral

Maximum 3.2 g daily.

Pain

Oral

For mild to moderate pain, maximum 3.2 g daily.

In fixed combination with hydrocodone, maximum 1 g of ibuprofen daily.

For self-medication of minor aches and pain, maximum 1.2 g daily. Self-medication should not exceed 10 days unless otherwise directed by a clinician.

In fixed combination with acetaminophen for self-medication of minor aches and pains, maximum 250 mg of ibuprofen every 8 hours. Self-medication should not exceed 10 days unless otherwise directed by a clinician.

For self-medication of migraine pain, maximum 400 mg in a 24-hour period unless otherwise directed by a clinician.

IV

Maximum 3.2 g in a 24-hour period.

Dysmenorrhea

Oral

Maximum 3.2 g daily.

For self-medication, maximum 1.2 g daily.

Fever

Oral

For self-medication, maximum 1.2 g daily. Self-medication should not exceed 3 days unless otherwise directed by a clinician.

IV

Maximum 3.2 g in a 24-hour period.

Special Populations

Renal Impairment

Avoid use in patients with advanced renal disease unless benefits expected to outweigh risk of worsening renal function. (See Renal Impairment under Cautions.)

CYP2C9 Poor or Intermediate Metabolizers

CYP2C9 poor metabolizers: Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines recommend initiating ibuprofen at a dosage that is 25–50% of the lowest recommended initial dosage and cautiously titrating to a clinically effective dosage, up to a dosage that is 25–50% of the maximum recommended dosage. Do not increase dosage until steady-state concentrations are attained (≥5 days after initial dose). Alternatively, consider a drug that is not metabolized by CYP2C9 or is not substantially affected by CYP2C9 genetic variants in vivo. (See Pharmacogenomic Considerations under Cautions.)

CYP2C9 intermediate metabolizers with a diplotype functional activity score (AS) of 1: CPIC guidelines recommend initiating ibuprofen at the lowest recommended initial dosage and cautiously titrating to a clinically effective dosage, up to the maximum recommended dosage.

Intermediate metabolizers with an AS of 1.5 may receive dosages recommended for normal metabolizers.

CPIC dosage recommendations apply to both OTC and prescription use of the drug.

Cautions for Ibuprofen

Contraindications

• Known hypersensitivity (e.g., anaphylaxis, serious dermatologic reactions) to ibuprofen or any ingredient in the formulation.

• History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.

• In the setting of CABG surgery.

IV Therapy for PDA

• Known or suspected untreated infection.

• Bleeding, especially active intracranial hemorrhage or GI bleeding; thrombocytopenia; coagulation defects.

• Known or suspected necrotizing enterocolitis.

• Substantial renal impairment.

• Congenital heart disease if patency of the ductus arteriosus is necessary for pulmonary or systemic blood flow (e.g., pulmonary atresia, severe tetralogy of Fallot, severe coarctation of the aorta).

Warnings/Precautions

Warnings

Cardiovascular Thrombotic Effects

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) increase the risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) in patients with or without cardiovascular disease or risk factors for cardiovascular disease.

Findings of FDA review of observational studies, meta-analysis of randomized controlled trials, and other published information indicate that NSAIAs may increase the risk of such events by 10–50% or more, depending on the drugs and dosages studied.

Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but the absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of their elevated baseline risk.

Increased risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.

In controlled studies, increased risk of MI and stroke observed in patients receiving a selective COX-2 inhibitor for analgesia in first 10–14 days following CABG surgery.

In patients receiving NSAIAs following MI, increased risk of reinfarction and death observed beginning in the first week of treatment.

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI; absolute mortality rate declined somewhat after the first post-MI year, but the increased relative risk of death persisted over at least the next 4 years.

Some systematic reviews of controlled observational studies and meta-analyses of randomized studies suggest naproxen may be associated with lower risk of cardiovascular thrombotic events compared with other NSAIAs. FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dosage for the shortest duration necessary.

Some clinicians suggest that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease. Avoid use in patients with recent MI unless benefits of therapy are expected to outweigh risk of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia. Contraindicated in the setting of CABG surgery.

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs. (See Specific Drugs under Interactions.)

GI Effects

Serious, sometimes fatal, GI toxicity (e.g., bleeding, ulceration, or perforation of esophagus, stomach, or small or large intestine) can occur with or without warning symptoms.

Risk for GI bleeding increased more than tenfold in patients with a history of peptic ulcer disease and/or GI bleeding who are receiving NSAIAs compared with patients without these risk factors.

Other risk factors for GI bleeding include concomitant use of oral corticosteroids, anticoagulants, aspirin, or SSRIs; longer duration of NSAIA therapy (however, short-term therapy is not without risk); smoking; alcohol use; older age; poor general health status; and advanced liver disease and/or coagulopathy.

Most spontaneous reports of fatal adverse GI effects involve geriatric or debilitated patients.

Frequency of NSAIA-associated upper GI ulcers, gross bleeding, or perforation is approximately 1% in patients receiving NSAIAs for 3–6 months and 2–4% at one year.

Use at lowest effective dosage for the shortest duration necessary.

Avoid use of more than one NSAIA at a time. (See Specific Drugs under Interactions.)

Avoid use of NSAIAs in patients at higher risk for GI toxicity unless expected benefits outweigh increased risk of bleeding; consider alternate therapies in high-risk patients and those with active GI bleeding.

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol; alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole) or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).

Monitor for GI ulceration and bleeding; even closer monitoring for GI bleeding recommended in those receiving concomitant low-dose aspirin for cardiac prophylaxis.

If serious adverse GI event suspected, promptly initiate evaluation and discontinue ibuprofen until serious adverse GI event ruled out.

Contraindicated in neonates with necrotizing enterocolitis.

Other Warnings and Precautions

Hepatic Effects

Severe, sometimes fatal, reactions including jaundice, fulminant hepatitis, liver necrosis, and hepatic failure reported rarely with NSAIAs.

Elevations of serum ALT or AST reported.

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results. Discontinue immediately and perform clinical evaluation if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur.

Hypertension

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events. Monitor BP during initiation of ibuprofen and throughout therapy.

Impaired response to ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and certain diuretics may occur. (See Specific Drugs under Interactions.)

Heart Failure and Edema

Fluid retention and edema reported.

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) may increase morbidity and mortality in patients with heart failure.

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema. (See Specific Drugs under Interactions.)

Manufacturer recommends avoiding use in patients with severe heart failure unless benefits of therapy are expected to outweigh risk of worsening heart failure; if used, monitor for worsening heart failure.

Some experts recommend avoiding use, whenever possible, in patients with reduced left ventricular ejection fraction and current or prior symptoms of heart failure.

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.

Potential for overt renal decompensation. Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist. (See Renal Impairment under Cautions.)

Correct dehydration before initiating ibuprofen therapy; monitor renal function during therapy in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia.

Renal insufficiency (including oliguria), increases in BUN, increases in S_cr, and renal failure reported in neonates. Decreases in urine output in ibuprofen-treated neonates noted on days 2–6 of life; compensatory increase in output noted on day 9.

Hyperkalemia

Hyperkalemia reported with NSAIAs, even in some patients without renal impairment; in such patients, effects attributed to a hyporenin-hypoaldosterone state.

Hypersensitivity Reactions

Anaphylactic reactions reported. Immediate medical intervention and discontinuance for anaphylaxis.

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); in patients with asthma but without known aspirin sensitivity, monitor for changes in manifestations of asthma.

Potentially fatal or life-threatening syndrome of multi-organ hypersensitivity (i.e., drug reaction with eosinophilia and systemic symptoms [DRESS]) reported in patients receiving NSAIAs. Clinical presentation is variable, but typically includes eosinophilia, fever, rash, lymphadenopathy, and/or facial swelling, possibly associated with other organ system involvement (e.g., hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis). Symptoms may resemble those of acute viral infection. Early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present in the absence of rash. If signs or symptoms of DRESS develop, discontinue the NSAIA and immediately evaluate the patient.

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning. Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).

Pharmacogenomic Considerations

CYP2C9 poor metabolizers: Ibuprofen metabolism may be decreased substantially, half-life may be prolonged, and higher plasma concentrations of the drug may increase likelihood and/or severity of adverse effects.

CYP2C9 intermediate metabolizers: Ibuprofen metabolism may be moderately or mildly reduced in those with an AS of 1 or 1.5, respectively. Higher plasma ibuprofen concentrations in intermediate metabolizers with an AS of 1 may increase likelihood of adverse effects. Presence of other factors affecting ibuprofen clearance (e.g., hepatic impairment, advanced age) also may increase risk of adverse effects in intermediate metabolizers. Further caution advised in patients carrying the CYP2C9*2 allele, since this allele is strongly linked to the decreased-function CYP2C8*3 allele, and CYP2C8 also contributes to ibuprofen metabolism.

Dosage reduction may be required based on CYP2C9 phenotype. (See CYP2C9 Poor or Intermediate Metabolizers under Dosage and Administration.)

Consult Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs for additional information on interpretation of CYP2C9 genotype testing.

Hematologic Effects

Anemia reported rarely. May be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. Determine hemoglobin concentration or hematocrit if signs or symptoms of anemia occur.

NSAIAs may increase the risk of bleeding. Patients with certain coexisting conditions (e.g., coagulation disorders) or receiving concomitant therapy with anticoagulants, antiplatelet agents, or serotonin-reuptake inhibitors may be at increased risk; monitor such patients for bleeding. (See Specific Drugs under Interactions.)

May inhibit platelet aggregation and prolong bleeding time.

Potential for spontaneous intraventricular hemorrhage in neonates. Observe premature infants for signs of bleeding.

Contraindicated in neonates who are bleeding and those with thrombocytopenia or coagulation defects.

Ocular Effects

Visual disturbances reported; ophthalmic evaluation recommended if visual changes occur.

Aseptic Meningitis

Aseptic meningitis reported rarely. Consider possibility that meningitis in a patient receiving ibuprofen is drug related.

Hyperbilirubinemia

Ibuprofen can displace bilirubin from serum albumin; caution in patients with elevated total bilirubin concentrations.

Individuals with Phenylketonuria

Motrin chewable tablets contain aspartame (NutraSweet), which is metabolized in the GI tract to provide 6 mg of phenylalanine for each 100-mg tablet.

Advil Junior Strength chewable tablets contain aspartame, which is metabolized to provide 4.2 mg of phenylalanine for each 100-mg tablet.

Diabetic Patients

Some commercially available preparations of ibuprofen may contain sucrose.

Use of Fixed Combinations

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Concomitant NSAIA Therapy

Concomitant use with other NSAIAs not recommended. (See Specific Drugs under Interactions.) Do not use multiple ibuprofen-containing preparations concomitantly.

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.

May mask certain signs of infection.

Obtain CBC and chemistry profile periodically during long-term use.

Specific Populations

Pregnancy

Use of NSAIAs during pregnancy at about ≥30 weeks’ gestation can cause premature closure of the fetal ductus arteriosus; use at about ≥20 weeks’ gestation associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment.

Effects of NSAIAs on the human fetus during third trimester of pregnancy include prenatal constriction of the ductus arteriosus, tricuspid incompetence, and pulmonary hypertension; nonclosure of the ductus arteriosus during the postnatal period (which may be resistant to medical management); and myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or renal failure, renal injury or dysgenesis potentially resulting in prolonged or permanent renal failure, oligohydramnios, GI bleeding or perforation, and increased risk of necrotizing enterocolitis.

Avoid use of NSAIAs in pregnant women at about ≥30 weeks’ gestation; if use required between about 20 and 30 weeks’ gestation, use lowest effective dosage and shortest possible duration of treatment, and consider monitoring amniotic fluid volume via ultrasound examination if treatment duration >48 hours; if oligohydramnios occurs, discontinue drug and follow up according to clinical practice. (See Advice to Patients.)

Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment observed, on average, following days to weeks of maternal NSAIA use; infrequently, oligohydramnios observed as early as 48 hours after initiation of NSAIAs. Oligohydramnios is often, but not always, reversible (generally within 3–6 days) following NSAIA discontinuance. Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation. In limited number of cases, neonatal renal dysfunction (sometimes irreversible) occurred without oligohydramnios. Some neonates have required invasive procedures (e.g., exchange transfusion, dialysis). Deaths associated with neonatal renal failure also reported. Limitations of available data (lack of control group; limited information regarding dosage, duration, and timing of drug exposure; concomitant use of other drugs) preclude 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; extent to which risks can be generalized to full-term infants is uncertain.

Animal data indicate important roles for prostaglandins in kidney development and endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, inhibitors of prostaglandin synthesis increased pre- and post-implantation losses; also impaired kidney development at clinically relevant doses.

No adequate and well-controlled studies of ibuprofen in pregnant women. No clear developmental effects observed in animal reproduction studies, although one study indicated an increase in membranous ventricular septal defects.

Effects of ibuprofen on labor and delivery not known. In animal studies, NSAIAs delayed parturition and increased stillbirths.

Lactation

Limited data indicate ibuprofen distributes into milk, resulting in infant doses of 0.06–0.6% of the maternal weight-adjusted daily dosage. Adverse effects on breast-fed infants or effects on milk production not reported to date.

Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for ibuprofen and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Fertility

NSAIAs may be associated with reversible infertility in some women. Reversible delays in ovulation observed in limited studies in women receiving NSAIAs; animal studies indicate that inhibitors of prostaglandin synthesis can disrupt prostaglandin-mediated follicular rupture required for ovulation.

Consider withdrawal of NSAIAs in women experiencing difficulty conceiving or undergoing evaluation of infertility.

Pediatric Use

Safety and efficacy of ibuprofen lysine established only in premature neonates receiving the drug for PDA. Long-term follow-up (>36 weeks postconception age) of these neonates has not been conducted. Effects of ibuprofen on neurodevelopmental outcome, growth, and other complications of prematurity (e.g., retinopathy of prematurity, chronic lung disease) not assessed. (See Contraindications under Cautions.)

Safety and efficacy of oral ibuprofen not established in infants <6 months of age.

Carefully monitor pediatric patients receiving dosages >30 mg/kg daily and those who had abnormal liver function test results associated with prior NSAIA therapy for signs and symptoms of early liver dysfunction.

Safety and efficacy of IV ibuprofen for pain relief and antipyresis in pediatric patients ≥6 months of age supported by evidence of fever reduction in an open-label study in hospitalized febrile pediatric patients, safety data from 3 studies in 143 pediatric patients ≥6 months of age receiving IV ibuprofen for pain relief or antipyresis, supportive data for other ibuprofen preparations labeled for use in pediatric patients, and evidence from adequate and well-controlled studies in adults. Efficacy of IV ibuprofen for pain relief or antipyresis not established in infants <6 months of age.

Risk of overdosage and toxicity (including death) in children <2 years of age receiving OTC preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection. Such preparations also may contain analgesics and antipyretics. Limited evidence of efficacy for these preparations in this age group; appropriate dosages not established. Therefore, FDA recommends not to use such preparations in children <2 years of age; safety and efficacy in older children currently under evaluation. Because children 2–3 years of age also are at increased risk of overdosage and toxicity, some manufacturers of oral OTC cough and cold preparations agreed to voluntarily revise the product labeling to state that such preparations should not be used in children <4 years of age. FDA recommends that parents and caregivers adhere to dosage instructions and warnings on the product labeling that accompanies the preparation and consult a clinician about any concerns.

Geriatric Use

Increased risk for serious adverse cardiovascular, GI, and renal effects. Fatal adverse GI effects reported more frequently in geriatric patients than younger adults. If anticipated benefits outweigh potential risks, initiate at lower end of dosing range and monitor for adverse effects.

Experience in those ≥65 years of age insufficient to determine whether they respond differently to IV ibuprofen than do younger adults. Select dosage with caution, starting at the low end of the dosage range, because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.

Renal Impairment

May hasten progression of renal dysfunction in patients with preexisting renal disease. Monitor patients with preexisting renal disease for worsening renal function.

Not evaluated in patients with severe renal impairment. Avoid use in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function; close monitoring of renal function advised if used.

Ibuprofen lysine contraindicated in neonates with substantially impaired renal function.

Common Adverse Effects

With oral ibuprofen therapy, dizziness, epigastric pain, heartburn, nausea, rash.

With IV ibuprofen therapy, nausea, flatulence, vomiting, headache, hemorrhage, and dizziness in adults; infusion site pain, vomiting, nausea, anemia, and headache in pediatric patients.

With IV ibuprofen lysine therapy, sepsis, anemia, bleeding, apnea, adverse GI effects, renal impairment, respiratory tract infection, dermatologic effects, hypoglycemia, hypocalcemia, respiratory failure.

Drug Interactions

No evidence of enzyme induction.

Specific Drugs

Ibuprofen Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration; peak plasma concentration usually attained within 1–2 hours.

Onset

Pain relief and/or antipyretic activity achieved within 1 hour.

Food

Food reduces peak plasma concentration by about 30–50% and delays time to reach peak plasma concentration by about 30–60 minutes but does not affect extent of absorption.

Distribution

Extent

Distributes into milk in small amounts.

Plasma Protein Binding

>99%.

Elimination

Metabolism

Almost completely metabolized, mainly via CYP-mediated oxidative metabolism to inactive metabolites. Metabolized mainly by CYP2C9 and to a lesser extent by CYP2C8. CYP3A4 contributes to clearance at high concentrations; CYP2C19 appears to play minor role. Approximately 10–15% of an ibuprofen dose metabolized to ibuprofen acyl glucuronide. Multiple uridine diphosphate-glucuronosyltransferase (UGT) isoenzymes can metabolize ibuprofen in vitro; further study needed to characterize the relative contributions of individual UGT isoenzymes to ibuprofen metabolism in vivo.

Elimination Route

Approximately 37 and 25% of dose excreted in urine as the 2 major metabolites, carboxyibuprofen and 2-hydroxyibuprofen (and their corresponding acyl glucuronides), respectively. Small amounts of other hydroxylated metabolites also recovered in urine. Little or no unchanged drug recovered in urine.

Half-life

1.8–2.4 hours.

Following oral administration, terminal elimination half-life reportedly similar in children and adults, but clearance in children may be affected by age or fever.

Following IV administration, elimination half-life shorter in pediatric patients than in adults: 1.5–1.6 hours in pediatric patients 2–16 years of age, 1.8 hours in those 6 months to <2 years of age.

Half-life 10-fold longer in neonates than in adults.

Stability

Storage

Oral

Capsules and Tablets

20–25°C; avoid excessive heat (>40°C).

Suspension

20–25°C.

Parenteral

Injection

Ibuprofen: 20–25°C (may be exposed to 15–30°C).

Ibuprofen lysine: 20–25°C (may be exposed to 15–30°C); store vials in carton until use to protect from light.

Actions

• Inhibits cyclooxygenase-1 (COX-1) and COX-2.

• Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.

• Permits closure of the ductus arteriosus in premature neonates by inhibiting prostaglandin synthesis.

Advice to Patients

• Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.

• When used for self-medication, importance of reading the product labeling.

• When used for self-medication, importance of using the lowest effective dosage and of not exceeding the recommended dosage or duration of therapy. (See Dosage and Administration.)

• When used for self medication, importance of reviewing the warning information provided by the manufacturer.

• Risk of serious cardiovascular events (e.g., MI, stroke). Importance of seeking immediate medical attention if signs and symptoms of a cardiovascular event (e.g., chest pain, dyspnea, weakness, slurred speech) occur.

• Risk of GI bleeding and ulceration. Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding develop. Inform patients receiving concomitant low-dose aspirin of the increased risk of GI bleeding.

• Risk of serious skin reactions, DRESS, and anaphylactic and other sensitivity reactions. Advise patients to stop taking the drug immediately if they develop any type of rash or fever and to promptly contact their clinician. Importance of seeking immediate medical attention if an anaphylactic reaction occurs.

• Risk of hepatotoxicity. Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.

• Risk of heart failure or edema; importance of reporting dyspnea, unexplained weight gain, or edema.

• Potential for ibuprofen to interfere with antiplatelet effect of low-dose aspirin. Importance of consulting clinician prior to taking low-dose aspirin concomitantly.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of avoiding NSAIA use beginning at 20 weeks’ gestation unless otherwise advised by a clinician; importance of avoiding NSAIAs beginning at 30 weeks’ gestation because of risk of premature closure of the fetal ductus arteriosus; monitoring for oligohydramnios may be necessary if NSAIA therapy required for >48 hours’ duration between about 20 and 30 weeks’ gestation.

• Advise women who are trying to conceive that NSAIAs may be associated with a reversible delay in ovulation.

• When used in premature infants with PDA, advise parents or caregivers that ibuprofen can alter signs of infection, inhibit clot formation, and irritate skin or tissues if leakage occurs at the administration site; importance of monitoring the infant for signs of infection, bleeding, and skin or tissue irritation.

• Advise patients using ibuprofen for self-medication of migraine headaches that headaches may worsen if the drug is used on ≥10 days per month.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs. Advise patients that concomitant use of other NSAIAs with ibuprofen provides little or no increase in efficacy but increases risk of GI toxicity, and is not recommended. Alert patients to the presence of NSAIAs, including ibuprofen, in many OTC preparations.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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