ibuprofen IV (Rx)

>10% (Caldolor)

Nausea (53-57%)

Anemia (20-36%)

Vomiting (15-22%)

Flatulence (7-16%)

Bacteremia (13%)

Hypoproteinemia (up to 13%)

Headache (9-11%)

>10% (NeoProfen)

Sepsis (43%)

Anemia (32%)

Total bleeding (32%; placebo 29%)

Intraventricular hemorrhage (29%; placebo 24%)

Apnea (28%; placebo 26%)

Non-necrotizing enterocolitis (22%; placebo 18%)

Respiratory infection (19%)

Skin lesion/irritation (16%)

Hypoglycemia (12%)

1-10% (Caldolor)

Hypertension (10%)

Hypernatremia (10%)

Serum blood urea nitrogen raised (10%)

Hypotension (7-10%)

Diarrhea (7-10%)

Hemorrhage (4-10%)

Bacterial pneumonia (3-7%)

Hypoalbuminemia (3-10%)

Serum lactate dehydrogenase level elevated (3-7%)

Thrombocytosis (3-7%)

Dizziness (4-6%)

Dyspepsia (1-4%)

Hypokalemia (1-4%)

Decreased hemoglobin (2-3%)

Wound hemorrhage (1-3%)

Cough (1-3%)

1-10% (NeoProfen)

Respiratory failure (10%)

Adrenal insufficiency (7%)

Hypernatremia (7%)

Increased blood urea (7%)

Renal impairment (6%)

Edema (4%)

Atelectasis (4%)

Decreased renal output (3%)

Increased blood creatinine (3%)

Renal failure (1%)

Postmarketing Reports

Pulmonary hypertension

Contraindications

Caldolor

• Hypersensitivity
• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
• Coronary artery bypass graft (CABG): Increased risk of MI and stroke if administered in the first 10-14 days following CABG

NeoProfen

• Untreated proven or suspected infection
• Congenital heart disease where PDA patency is necessary for satisfactory pulmonary or systemic blood flow (eg, pulmonary atresia, severe tetralogy of Fallot, severe coarctation of the aorta)
• Bleeding, especially active intracranial hemorrhage or GI bleeding
• Thrombocytopenia; coagulation defects
• Necrotizing enterocolitis
• Significant renal impairment

Cautions

Caldolor

• Increased risk for serious CV thrombotic events, myocardial infarction (MI), and stroke (use lowest effective dose for shortest duration possible); additionally, increased MI and stroke if administered in the first 10-14 days following CABG (see Contraindications)
• Risk of GI ulceration, bleeding, and perforation
• May cause borderline LFT elevations; rare reports of notable ALT or AST (ie, 3xULN) or severe hepatic reactions (eg, jaundice, fulminant hepatitis, liver necrosis, hepatic failure)
• May cause new onset hypertension, or exacerbation of existing hypertension
• Fluid retention and edema observed; caution in patients with heart failure
• Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include the elderly, or those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, and individuals taking diuretics, ACE inhibitors, or ARBs
• Anaphylactoid reactions reported (see Contraindications)
• Serious skin reactions may occur (eg, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Avoid in pregnancy after 30 weeks gestation; associated with premature closure of the ductus arteriosus
• Diminishes utility of inflammation and fever as diagnostic signs for infection
• Concentrated formulation (ie, 100 mg/mL) must be diluted prior to use; infusing undiluted may result in hemolysis
• Patients with asthma may have aspirin-sensitive asthma; use of aspirin or NSAIDs may cause severe bronchospasm in these patients
• Blurred or diminished vision, scotomata, and changes in color vision reported with oral ibuprofen
• Aseptic meningitis with fever and coma observed with oral ibuprofen therapy

NeoProfen

• Diminishes utility of inflammation and fever as diagnostic signs for infection
• Inhibits platelet aggregation; caution with underlying hemostatic defects (see Contraindications)
• Displaces bilirubin from albumin binding-sites
• Administer cautiously to avoid extravasation

Pregnancy

Avoid use in pregnant women start at 30 weeks’ gestation; NSAID use during third trimester increases risk of premature closure of the fetal ductus arteriosus

There are no adequate and well-controlled studies in pregnant women; data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive

Animal studies

• 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 (eg, ibuprofen), resulted in increased pre- and post-implantation loss
• Advise pregnant women of potential fetal risk

Clinical considerations

• There are no studies on effects during labor or delivery
• In animal studies, NSAIDs, including ibuprofen, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth

Lactation

No lactation studies have been conducted; however, limited published literature reports that, following oral administration, ibuprofen is present in human milk at relative infant doses of 0.06-0.6% of the maternal weight-adjusted daily dose

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.

Mechanism of Action

Elicits anti-inflammatory, analgesic, and antipyretic activity

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

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

Absorption

Peak Plasma Concentration: 39.2-72.6 mcg/mL (Caldolor)

AUC: 109.3-192.8 mcg•h/mL (Caldolor)

Distribution

Protein Bound: >99% (saturable at >20 mcg/mL)

Vd: 320 mL/kg (NeoProfen)

Metabolism

Racemic mixture of R- and S-isomers; in vivo and in vitro studies indicate the S-isomer is active and the R-form, while thought to be pharmacologically inactive, is slowly and incompletely (~60%) interconverted into the active S species in adults

Hepatic CYP2C9 (primarily); CYP2C19 substrate

Metabolites: (+)-2-[4'-(2-hydroxy-2-methylpropyl) phenyl] propionic acid (metabolite A), (+)-2-[4'-(2-carboxypropyl) phenyl] propionic acid (metabolite B)

Elimination

Half-life: 2.22-2.44 hr (Caldolor); >10 times that of adults (neonates), 43.1 hr (3 days old) and 26.8 hr (5 days old)

Renal clearance: 3 mL/kg/hr (NeoProfen); increases rapidly postnatally by 0.5 mL/kg/hr per day

Excretion: Urine (predominantly) and bile

IV Preparation

Caldolor

• 800 mg/8mL (100 mg/mL) must be diluted

  • Dilute to a final concentration of ≤4 mg/mL in 0.9% NaCl, D5W or LR
  • 100 mg dose: Dilute 1 mL in at least 100 mL of diluent
  • 200 mg dose: Dilute 2 mL in at least 100 mL of diluent
  • 400 mg dose: Dilute 4 mL in at least 100 mL of diluent
  • 800 mg dose: Dilute 8 mL in at least 200 mL of diluent

• 800 mg/200 mL (4 mg/mL) ready-to-use bags

  • No further dilution required
  • Ready-to use bags intended for 800 mg doses only

NeoProfen

• Dilute in dextrose or 0.9% NaCl
• Administer within 30 minutes of dilution

IV Administration

Caldolor

• Adults: Infuse over at least 30 minutes
• Pediatric patients aged 6 mo to 17 yr: Infuse over at least 10 minutes

NeoProfen

• Infuse over 30 minutes
• Use IV port nearest to insertion site
• Do NOT coadminister with TPN in same line (allow 15 min discontinuation of TPN if necessary)
• Discard unused portion - no preservatives

Storage

NeoProfen: Store vial at room temperature, protect from light

Caldolor

• Unopened vials or RTU bags: Store at controlled room temperature 20-25C (68-77F); excursions permitted to 15-30C (59-86F)
• Diluted solutions: Stable for up to 24 hr at ambient temperature (~20-25C) and room lighting