ibuprofen (Advil, Motrin, PediaCare Children's Pain Reliever/Fever Reducer IB, PediaCare Infant's Pain Reliever/Fever Reducer IB)

Dosing and uses of Advil, Motrin (ibuprofen)

• Adult
• Pediatric

 

Adult dosage forms and strengths

tablet

• 100mg
• 200mg
• 400mg (Rx)
• 600mg (Rx)
• 800mg (Rx)

capsule

• 200mg

tablet, chewable

• 50mg
• 100mg

oral suspension

• 100mg/5mL
• 40mg/mL

 

Pain/Fever/Dysmenorrhea

OTC: 200-400 mg PO q4-6hr; not to exceed 1.2 g unless directed by physician

Prescription: 400-800 mg PO/IV q6hr

 

Inflammatory Disease

400-800 mg PO q6-8hr; not to exceed 3.2 g/day

 

Osteoarthritis

300 mg, 400 mg, 600 mg, or 800 mg PO q6-8hr; not to exceed 3.2 g/day

Monitor for gastrointestinal (GI) risks

 

Rheumatoid Arthritis

300 mg, 400 mg, 600 mg, or 800 mg PO q6-8hr; not to exceed 3200 mg/day

Monitor for GI risks

 

Dosage modifications

Significantly impaired renal function: Monitor closely; consider reduced dosage if warranted

Severe hepatic impairment: Avoid use

 

Pediatric dosage forms and strengths

tablet

• 100mg
• 200mg
• 400mg (Rx)
• 600mg (Rx)
• 800mg (Rx)

capsule

• 200mg

tablet, chewable

• 50mg
• 100mg

oral suspension

• 100mg/5mL
• 40mg/mL

 

Fever

6 months to 12 years

5-10 mg/kg/dose PO q6-8hr; not to exceed 40 mg/kg/day

 

Pain

4-10 mg/kg/dose PO q6-8hr; not to exceed 40 mg/kg/day

 

Juvenile Idiopathic Arthritis

30-50 mg/kg/24hr PO divided q8hr; not to exceed 2.4 g/day

 

Patent Ductus Arteriosus

See ibuprofen IV drug monograph

 

Cystic Fibrosis (Off-label)

<4 years: Safety and efficacy not established

≥4 years: PO administration q12hr, adjusted to maintain serum levels of 50-100 mcg/mL; may slow disease progression in younger patients with mild lung disease

 

Dosing Considerations

Potential toxic dose in children <6 years: 200 mg/kg

 

Advil, Motrin (ibuprofen) adverse (side) effects

1-10%

Dizziness (3-9%)

Epigastric pain (3-9%)

Heartburn (3-9%)

Constipation (1-3%)

Nausea (3-9%)

Rash (3-9%)

Tinnitus (3-9%)

Edema (1-3%)

Fluid retention (1-3%)

Headache (1-3%)

Vomiting (1-3%)

 

<1%

Acute renal failure (sometimes with acute tubular necrosis or hyperkalemia, polyuria, azotemia, cystitis, hematuria, decreased creatinine clearance, elevations in blood urea nitrogen (BUN) or creatinine without other manifestations of renal failure)

Agranulocytosis

Aplastic anemia

Erythema multiforme

Erythematous macular rashes

Exfoliative dermatitis

Hemolytic anemia (with or without positive direct antiglobulin test results)

Neutropenia

Thrombocytopenia (with or without purpura)

Toxic epidermal necrolysis (Lyell syndrome) and photosensitivity reactions

 

Warnings

Black box warnings

Cardiovascular risk

• Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal
• Risk may increase with duration of use
• Patients with existing cardiovascular disease or risk factors for such disease may be at greater risk
• NSAIDs are contraindicated for perioperative pain in setting of coronary artery bypass graft (CABG) surgery

Gastrointestinal risk

• NSAIDs increase risk of serious GI adverse events, including bleeding, ulceration, and gastric or intestinal perforation, which can be fatal
• GI adverse events may occur at any time during use and without warning symptoms
• Elderly patients are at greater risk for serious GI events

 

Contraindications

Absolute

• Aspirin allergy
• Perioperative pain in setting of coronary artery bypass graft (CABG) surgery
• Preterm infants with untreated proven or suspected infection; bleeding with active intracranial hemorrhage or GI bleed; thtombocytopenia, coagulation defects, proven or necrotizing enterocolitis, significant renal impairment, congenital heart disease where patency or the PDA is necessary for pulmonary or systemic blood flow

 

Cautions

Use caution in asthma (bronchial), cardiac disease, congestive heart failure (CHF), hepatic or renal impairment, hypertension. bleeding disorder, duodenal/gastric/peptic ulcer, stomatitis, systemic lupus erythematosus (SLE), ulcerative colitis, upper GI disease, late pregnancy (may cause premature closure of ductus arteriosus)

Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include elderly individuals; those with impaired renal function, hypovolemia, heart failure, liver dysfunction, or salt depletion; and those taking diuretics, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers

Junior Advil (100 mg): Doses higher than recommended may cause stomach bleeding

May cause serious adverse reactions, including exfoliative dermatitis, toxic epidermal necrolysis, Steven's Johnson syndrome reported

Children's and Junior Advil (50 mg, 100 mg): May cause severe and persistent sore throat

Fever, rash, abdominal pain, nausea, liver dysfunction, and meningitis have occurred in patients with collagen-vascular disease, especially SLe

Blurred vision, scotomate, and changes in color vision reported; discontinue therapy if symptoms occur

Platelet aggregation and adhesion may be decreased; monitor patients with coagulation disorders receiving the therapy

Risk of hyperkalemia may increase in patients with diabetes, the elderly, renal disease, or with concomitant use of agents that can induce hyperkalemia including ACE inhibitors; monitor potassium closely

May cause drowsiness and dizziness; may impair physical or mental abilities to operate heavy machinery or driving

Heart Failure (HF) risk

• NSAIDS have the potential to trigger HF by prostaglandin inhibition that leads to sodium and water retention, increased systemic vascular resistance, and blunted response to diuretics
• NSAIDS should be avoided or withdrawn whenever possible
• AHA/ACC Heart Failure Guidelines; Circulation. 2016; 134

 

Pregnancy and lactation

Pregnancy category: C; D at ≥30 weeks' gestation; may cause premature closure of ductus arteriosus

Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks' gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in approximately 7.5% of cases of spontaneous abortions and in approximately 2.6% of controls

Lactation: Drug excreted into breast milk; use not recommended (American Academy of Pediatrics committee states that drug is compatible with nursing)

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Advil, Motrin (ibuprofen)

Mechanism of action

Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclo-oxygenase (COX) isoenzymes, COX-1 and COX-2

May inhibit chemotaxis, alter lymphocyte activity, decrease proinflammatory cytokine activity, and inhibit neutrophil aggregation; these effects may contribute to anti-inflammatory activity

 

Absorption

Rapidly absorbed (85%)

Bioavailability: 80-100%

Onset: 30-60 min

Duration: 4-6 hr

Peak plasma time (adults)

• Conventional tablet: 120 min
• Chewable tablet: 62 min
• Oral suspension: 47 min

Peak plasma time (febrile children)

• Chewable tablet: 86 min
• Oral suspension: 58 min

Peak plasma concentration

• Conventional tablet: 20 mcg/mL
• Chewable tablet: 15 mcg/mL
• Oral suspension: 19 mcg/mL

 

Distribution

Protein bound: 90-99%; concentrations >20 mcg/mL

Vd: 0.12 L/kg (adults); 0.164 L/kg (children)

 

Metabolism

Rapidly metabolized in liver (primarily by CYP2C9; CYP2C19 substrate) via oxidation to inactive metabolites

Metabolites

• Metabolite A: (+)-2-[4'-(2-hydroxy-2-methylpropyl) phenyl] propionic acid
• Metabolite B: (+)-2-[4'-(2-carboxypropyl) phenyl] propionic acid

 

Elimination

Half-life: 2-4 hr (adults); 1.6 hr (children 3 mon to 1 year; 35-51 hr (day 3), 20-33 hr (day 5)

Excretion: Urine (50-60%; <10% unchanged); remainder in feces within 24 hr

 

Administration

Instructions

Take with food or 8-12 oz of water to avoid GI effects