CALDOLOR (ibuprofen)

There are 5 contraindications. Absolute contraindication.

Contraindication List
Aspirin exacerbated respiratory disease
Hemorrhagic stroke
Post-operative from CABG surgery
Pregnancy
Renal transplant

There are 21 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute myocardial infarction
Alcohol use disorder
Chronic heart failure
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
CYp2c9 intermediate metabolizer (activity score 1)
CYp2c9 poor metabolizer
Edema
Gastrointestinal hemorrhage
Gastrointestinal perforation
Gastrointestinal ulcer
Hemorrhage
History of kidney donation
Increased risk of bleeding
Increased risk of bleeding due to coagulation disorder
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Nephrectomy
Systemic mastocytosis
Thrombocytopenic disorder
Thrombotic disorder
Tobacco smoker

There are 4 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Anemia
Dehydration
Hypertension
Systemic lupus erythematosus

There are 31 severe adverse reactions.

More Frequent	Less Frequent
Hemorrhage	Abnormal hepatic function tests Anemia Hypernatremia Hypokalemia Thrombocytosis

Rare/Very Rare

Acute eruptions of skin Acute myocardial infarction Allergic dermatitis Anaphylaxis Bacterial sepsis Bullous dermatitis Cerebrovascular accident DRESS syndrome Esophageal perforation Exfoliative dermatitis Gastric ulcer Gastrointestinal hemorrhage Gastrointestinal perforation Gastrointestinal ulcer Hepatic failure Hepatic necrosis Hepatitis Hyperkalemia Jaundice Kidney disease with reduction in glomerular filtration rate (GFr) Neutropenic disorder Non-infective meningitis Stevens-johnson syndrome Toxic epidermal necrolysis Worsening of chronic heart failure

There are 19 less severe adverse reactions.

More Frequent	Less Frequent
Dizziness Flatulence Headache disorder Nausea Vomiting	Acute abdominal pain Bleeding from wound Cough Diarrhea Dyspepsia Edema Eosinophilia Hypertension Hypoalbuminemia Hypoproteinemia Peripheral edema Urinary retention

Rare/Very Rare
Hypotension Injection site sequelae

Use of NSAIAs during pregnancy at about 30 weeks' gestation or later can cause premature closure of the fetal ductus arteriosus, and use at about 20 weeks' gestation or later has been associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, use of NSAIAs should be avoided in pregnant women at about 30 weeks' gestation or later; if NSAIA therapy is necessary between about 20 and 30 weeks' gestation, the lowest effective dosage and shortest possible duration of treatment should be used. Monitoring of amniotic fluid volume via ultrasound examination should be considered if the duration of NSAIA treatment exceeds 48 hours; if oligohydramnios occurs, the drug should be discontinued and follow-up instituted according to clinical practice.

Pregnant women should be advised to avoid use of NSAIAs beginning at 20 weeks' gestation unless otherwise advised by a clinician; they also should be informed that NSAIAs should be avoided beginning at 30 weeks' gestation because of the risk of premature closure of the fetal ductus arteriosus and that monitoring for oligohydramnios may be necessary if NSAIA therapy is required for longer than 48 hours' duration between about 20 and 30 weeks of gestation. Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment has been observed, on average, following days to weeks of maternal NSAIA use, although oligohydramnios has been observed infrequently as early as 48 hours after initiation of NSAIA therapy. Oligohydramnios is often, but not always, reversible following discontinuance of NSAIA therapy.

Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation. A limited number of case reports have described maternal NSAIA use and neonatal renal dysfunction, in some cases irreversible, without oligohydramnios. Some cases of neonatal renal dysfunction have required treatment with invasive procedures such as exchange transfusion or dialysis.

Methodologic limitations of these postmarketing studies and case reports include lack of a control group; limited information regarding dosage, duration, and timing of drug exposure; and concomitant use of other drugs. These limitations preclude establishing 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, and the extent to which certain reported risks can be generalized to full-term infants is uncertain.

Animal data indicate that prostaglandins have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, inhibitors of prostaglandin synthesis, such as ibuprofen, were associated with increased preimplantation and postimplantation losses. Prostaglandins also have an important role in fetal kidney development.

In animal studies, inhibitors of prostaglandin synthesis impaired kidney development at clinically relevant doses. There are no adequate and well-controlled studies of ibuprofen in pregnant women. In animal reproduction studies, no clear developmental effects were observed in rabbits or rats given ibuprofen throughout the gestational period at dosages up to 0.4

or 0.5 times, respectively, the maximum recommended human dosage (MRHD). An increase in membranous ventricular septal defects was reported in rats given ibuprofen on gestation days 9 and 10 at a dosage of 0.8

times the MRHD. The effects of ibuprofen on labor and delivery are unknown. In studies in rats, drugs that inhibit prostaglandin synthesis, including NSAIAs, delayed parturition and increased the incidence of stillbirth.

Limited data indicate that ibuprofen is distributed into milk, resulting in infant exposures of 0.06-0.6% of the maternal weight-adjusted daily dosage.

Adverse effects on breast-fed infants or effects on milk production have not been reported to date. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for ibuprofen and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Geriatric patients are at increased risk for NSAIA-associated serious adverse cardiovascular, GI, and renal effects. Many of the spontaneous reports of fatal adverse GI effects in patients receiving NSAIAs involve geriatric individuals. If the anticipated benefits of ibuprofen therapy outweigh the potential risks, ibuprofen should be initiated at the lower end of the dosing range and patients should be monitored for adverse effects.

Clinical studies of IV ibuprofen did not include sufficient numbers of patients >=65 years of age to determine whether geriatric patients respond differently than younger adults. Dosage should be selected with caution, starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, and/or cardiac function and concomitant disease and drug therapy observed in the elderly.