Ibuprofen intravenous (IV)

Ibuprofen intravenous (IV) is a non-steroidal anti-inflammatory drug (NSAID) administered into the vein (intravenous). Ibuprofen IV is used in the management of pain and fever and to treat patent ductus arteriosus (PDA), a condition in newborn babies in which a fetal connection between the aorta and pulmonary artery that normally closes at birth, remains open.

Ibuprofen works by blocking the activity of enzymes known as cyclooxygenases (COX-1 and COX-2), essential for biosynthesis of prostaglandin. Prostaglandins are fatty compounds that regulate many processes in the body including inflammation, smooth muscle function, and blood flow and clotting processes.

Ibuprofen slows down blood clotting function by inhibiting platelet aggregation. It is not known how exactly ibuprofen IV promotes the closure of patent ductus arteriosus. Intravenous ibuprofen controls inflammation and relieves pain and fever by:

• Preventing the movement of inflammatory cells to the inflammation site
• Blocking the release of proinflammatory proteins (cytokines)

Uses of ibuprofen IV include:

• Reduction of fever
• Management of mild-to-moderate pain, or for moderate-to-severe pain as an adjunct to opioid pain relievers (analgesics) in adults and children 6 months or older
• 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

The ibuprofen IV brand Caldolor is used to treat pain and fever in adults and pediatric patients, and NeoProfen is used for patent ductus arteriosus in premature infants.

Cardiovascular risk:

• Ibuprofen IV may increase the risk of serious cardiovascular clotting (thrombotic) events, heart attack (myocardial infarction), and stroke, which can be fatal
• Risk for the above may increase with duration of use
• Do not use ibuprofen IV in patients with existing cardiovascular disease or risk factors for such disease, they may have greater cardiovascular risk
• Ibuprofen IV can lead to new onset or exacerbation of high blood pressure (hypertension)

Gastrointestinal risk:

• Ibuprofen IV can cause serious gastrointestinal (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

Caldolor

• Do not administer in patients with known hypersensitivity to ibuprofen or any of its components
• Do not administer in patients with history of asthma, hives or other allergic reactions to aspirin or other NSAIDs
• Do not use in the setting of coronary artery bypass graft (CABG) surgery

NeoProfen

Do not administer NeoProfen to preterm infants with the following conditions:

• Untreated proven or suspected infection
• Bleeding with active intracranial hemorrhage or gastrointestinal (GI) bleed
• Low platelet count (thrombocytopenia)
• Coagulation defects
• Proven or suspected intestinal inflammation with tissue death (necrotizing enterocolitis)
• Significant renal impairment
• Congenital heart disease where patency of the ductus arteriosus is necessary for pulmonary or systemic blood flow

Common side effects of ibuprofen IV include:

Caldolor

• Nausea
• Vomiting
• Gas (flatulence)
• Headache
• Low red blood cell count (anemia)
• Presence of bacteria in blood (bacteremia)
• Low protein levels in blood (hypoproteinemia)
• High blood pressure (hypertension)
• Increased sodium levels (hypernatremia)
• Elevated blood urea nitrogen (BUN)

NeoProfen

• Sepsis
• Anemia
• Total bleeding
• Bleeding in the ventricular space in the brain (intraventricular hemorrhage)
• Cessation of breathing (apnea)
• Intestinal inflammation without tissue death (non-necrotizing enterocolitis)
• Respiratory infection
• Skin lesion/irritation
• Low blood glucose levels (hypoglycemia)
• Respiratory failure

Less common side effects of ibuprofen IV include:

Caldolor

• Low blood pressure (hypotension)
• Diarrhea
• Hemorrhage
• Bacterial pneumonia
• Low albumin in blood (hypoalbuminemia)
• Elevated blood levels of the enzyme lactate dehydrogenase (LDH)
• Increased platelet count (thrombocytosis)
• Dizziness
• Indigestion (dyspepsia)
• Low potassium in blood (hypokalemia)
• Decreased hemoglobin
• Wound hemorrhage
• Cough

NeoProfen

• Adrenal insufficiency
• Hypernatremia
• Increased blood urea
• Impairment of kidney function
• Swelling (edema)
• Partial or complete collapse of a lung or part of a lung (atelectasis)
• Decreased urine output
• Increased blood creatinine
• Kidney failure

Other side effects of ibuprofen IV include:

• Pulmonary hypertension
• Drug reaction with eosinophilia and systemic symptoms (DRESS)

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable solution

• 800mg/8mL (100mg/mL single-dose vial, Caldolor); must dilute further
• 800mg/200mL (4mg/mL ready-to-use bag, Caldolor)

Injectable solution, ibuprofen lysine

• 10mg/mL (2mL single-dose vial, Neoprofen)

Adult

Pain

• Caldolor: 400-800 mg IV every 6 hour as needed; not to exceed 3200 mg/day

Fever

Caldolor: 400 mg IV, THEN

• 400 mg IV every 4-6 hours or 100-200 mg every 4 hours as needed; not to exceed 3200 mg/day

Dosing Considerations

• Patients must be well hydrated before administration

Pediatric

Pain and/or Fever

Caldolor

Children younger than 6 months:

• Safety and efficacy not established

Children 6 months to 12 years:

• 10 mg/kg IV every 4-6 hour as needed; not to exceed 400 mg/dose; maximum daily dose is 40 mg/kg or 2400 mg, whichever is less

Children 12-17 years:

• 400 mg IV every 4-6 hour as needed; do not exceed 2,400 mg, whichever is less, total daily dose in pediatric patients aged below 17 years

Patent Ductus Arteriosus

NeoProfen

• Initial dose: 10 mg/kg IV, THEN
• Additional 2 doses of 5 mg/kg each, at 24 and 48 hours
• In case of renal dysfunction, withhold 2nd/3rd dose until renal function is normal
• If ductus arteriosus fails to close, then a second course of ibuprofen IV, alternative pharmacological therapy, or surgery may be needed

• Overdose of intravenous ibuprofen may cause lethargy, drowsiness, nausea, vomiting and upper abdominal pain, which may be treated with supportive care.
• Gastrointestinal ulceration and hemorrhage may also occur and the patient must be monitored for several days in the event of overdose.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe Interactions of ibuprofen IV include: None
• Ibuprofen IV has serious interactions with at least 25 drugs that include:
  • aminolevulinic acid
  • apixaban
  • aspirin
  • benazepril
  • captopril
  • enalapril
  • fosinopril
  • ketorolac
  • lisinopril
  • meclofenamate
  • methotrexate
  • methyl aminolevulinate
  • moexipril
  • naproxen
  • oxaprozin
  • pemetrexed
  • perindopril
  • quinapril
  • ramipril
  • tacrolimus
  • trandolapril
• Ibuprofen has moderate interactions with at least 244 different drugs.
• Ibuprofen has mild interactions with at least 67 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no adequate and well-controlled studies of ibuprofen use in pregnancy, labor and delivery.
• Avoid using ibuprofen up to 20 weeks of gestation. Animal studies indicate an increased risk for loss of pregnancy in early stages because ibuprofen inhibits the synthesis of prostaglandin.
• Limit dose and duration of use between about 20 and 30 weeks of gestation.
• Avoid ibuprofen use at about 30 weeks of gestation and later in pregnancy, it may cause premature closure of ductus arteriosus and fetal renal dysfunction.
• Animal studies show that ibuprofen may delay delivery and increase the incidence of stillbirth.
• No lactation studies have been conducted. Ibuprofen may be excreted in breast milk at extremely low levels. Ibuprofen has a short half-life and is considered safe in infants in doses much higher than those excreted in breast milk.

Caldolor

• May cause liver enzyme elevation and other liver reactions.
• May cause new onset or exacerbation of high blood pressure (hypertension).
• May cause fluid retention and edema and must be used with caution in patients with congestive heart failure.
• Long-term administration of NSAIDs may result in kidney damage or injury; patients at the greatest risk include elderly individuals, those with impaired renal function, low blood volume (hypovolemia), heart failure, liver dysfunction, or salt depletion; and those taking medication such as diuretics, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers.
• Can cause severe skin reactions such as exfoliative dermatitis, toxic dermal necrolysis and Stevens-Johnson syndrome.
• Reduces the usefulness of inflammation and fever as diagnostic signs for infection.
• Can cause bronchospasm in patients with asthma or aspirin-sensitive asthma
• May cause blurred vision, partial loss of vision/blind spot or changes in color vision.

NeoProfen

• Must be administered carefully to avoid leakage from the vein (extravasation).
• Must be used with extra caution in infants with controlled infection or at risk for infection; NeoProfen may alter the usual signs of infection.
• Must be used with caution in infants with bleeding disorders, may prolong bleeding time.
• Must be used with caution in infants with elevated total bilirubin (neonatal jaundice), NeoProfen may increase the level of free bilirubin by displacing it from albumin binding sites.
• There are no long-term evaluations of NeoProfen’s effects on developmental issues associated with prematurity.
• Drug reaction with eosinophilia and systemic symptoms (DRESS)
• DRESS has been reported in patients taking NSAIDs, some of which have been fatal or life-threatening. DRESS may present with fever, rash, swollen lymph nodes (lymphadenopathy), and/or facial swelling.