Dosing and uses of Caldolor, NeoProfen (ibuprofen IV)
Adult dosage forms and strengths
IV solution
- 100mg/mL (Caldolor)
Pain
Indicated for management of mild-to-moderate pain, or for moderate-to-severe pain as an adjunct to opioid analgesics
Caldolor: 400-800 mg IV infused over 30 minutes q6hr PRN; not to exceed 4200 mg/day
Fever
Caldolor: 400 mg IV infused over 30 minutes, THEn
400 mg q4-6hr or 100-200 mg q4hr PRN; not to exceed 4200 mg/day
Dosing Considerations
Patients must be well hydrated before administration
Must further dilute Caldolor before administration (undiluted solution may result in hemolysis)
Pediatric dosage forms and strengths
IV solution
- 10mg/mL (NeoProfen)
- 100mg/mL (Caldolor)
Patent Ductus Arteriosus
Indicated to close a clinically significant patent ductus arteriosus (PDA) in premature infants weighing between 500-1500 g, who are no more than 32 weeks gestational age when usual medical management is ineffective
Initial NeoProfen dose: 10 mg/kg IV, THEn
Additional 2 NeoProfen doses of 5 mg/kg each, after 24 and 48 hr
If renal dysfunction, withhold 2nd/3rd dose until renal function normaL
If ductus arteriosus fails to close, then a second course of ibuprofen IV, alternative pharmacological therapy, or surgery may be needed
Pain
Caldolor
- Indicated for management of mild-to-moderate pain and the management of moderate-to-severe pain as an adjunct to opioid analgesics
- <6 months: Safety and efficacy not established
- 6 months to <12 years: 10 mg/kg IV q4-6 hr prn; not to exceed 400 mg/dose; maximum daily dose is 40 mg/kg or 2400 mg, whichever is less
- 12-17 years: 400 mg IV q4-6 hr prn
- Do not exceed 40 mg/kg or 2,400 mg, whichever is less, total daily dose in pediatric patients aged <17 yr
- Must dilute solution; undiluted solution may result in hemolysis (see IV preparation)
Fever
Caldolor
- Indicated for management of mild-to-moderate pain and the management of moderate-to-severe pain as an adjunct to opioid analgesics
- <6 months: Safety and efficacy not established
- 6 months to <12 years: 10 mg/kg IV q4-6 hr prn; not to exceed 400 mg/dose; maximum daily dose is 40 mg/kg or 2400 mg, whichever is less
- 12-17 years: 400 mg IV q4-6 hr prn
- Do not exceed 40 mg/kg or 2,400 mg, whichever is less, total daily dose in pediatric patients aged <17 yr
- Must dilute solution; undiluted solution may result in hemolysis (see IV preparation)
Caldolor, NeoProfen (ibuprofen IV) adverse (side) effects
>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
Warnings
Black box warnings
These warnings are specific for Caldolor
Cardiovascular Risk
- 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 risk factors for or with existing cardiovascular disease may be at greater risk
- NSAIDs are contraindicated for perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (increased risk of MI and stroke)
Gastrointestinal Risk
- NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, and
- perforation of the stomach or intestines, 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
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
- 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 and lactation
Pregnancy category: C; D from 30 weeks of gestation onward, may cause premature closure of the ductus arteriosus
The 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. (CMAJ, September 6, 2011; DOI:10.1503/cmaj.110454)
Lactation: excreted into breast milk; not recommended (AAP Committee states "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 Caldolor, NeoProfen (ibuprofen IV)
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
Administration
IV Preparation
Caldolor
- 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
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
Caldolor: Store unopened vial at room temperature; diluted solutions are stable for up to 24 hr at room temperature and room lighting
NeoProfen: Store vial at room temperature, protect from light
