1 Adverse Reaction Overview Clinical Trial & Post-Market Adverse Drug Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. The most common adverse reactions encountered with nonsteroidal anti-inflammatory drugs are gastrointestinal, of which gastric or duodenal ulcer, with or without bleeding, is the most severe.
Fatalities have occurred, particularly in the elderly. APO-IBUPROFEN and APO-IBUPROFEN CAPLET (Ibuprofen tablets) Page 17 of 48 Experience reported with prescription use of ibuprofen has included the following adverse reactions.
Note:
Reactions listed below under Causal Relationship Unknown are those where a causal relationship could not be established; however, in these rarely reported events, the possibility of a relationship to ibuprofen also cannot be excluded.
Adverse Effect Common (>1% but <10%) Less Common (<1%) Incidence 3-9% Incidence 1-3% Allergic • anaphylaxis (See 2 CONTRAINDICATIONS) Also reported but with unknown causal relationship, rarely: • fever • serum sickness • lupus erythematosus syndrome Cardiovascular • congestive heart failure in patients with marginal cardiac function • elevated blood pressure • Conditions such as congestive heart failure and hypertension may be aggravated by sodium retention and edema caused by ibuprofen in such patients • myocardial infarction • stroke (cerebrovascular accident) Also reported but with unknown causal relationship, rare cases of: • arrhythmias (sinus tachycardia, sinus bradycardia, palpitations) • hemorrhage (non-GI) • Kounis syndrome Central Nervous System • dizziness • headache • nervousness • drowsiness/som nolence • depression • insomnia Also reported but with unknown causal relationship: • paresthesias • hallucinations APO-IBUPROFEN and APO-IBUPROFEN CAPLET (Ibuprofen tablets) Page 18 of 48 Adverse Effect Common (>1% but <10%) Less Common (<1%) Incidence 3-9% Incidence 1-3% • dream abnormalities • aseptic meningitis has been reported in patients with systemic lupus erythematosus or other connective tissue disease • aseptic meningitis and meningioencephalitis, in one case accompanied by eosinophilia in the cerebrospinal fluids, has been reported in patients who took ibuprofen intermittently and did not have any connective tissue disease • cognitive dysfunction has been observed in elderly patients who took ibuprofen • psychomotor hyperactivity Immune System Disorders Rare: • hypersensitivity Dermatologic • rash (including maculopapular type) • pruritis • vesiculobullous eruptions • urticaria • erythema • erythema multiforme • angioedema • fixed eruption Also reported but with unknown causal relationship: • alopecia • Stevens-Johnson Syndrome • toxic epidermal necrolysis • Drug reaction with eosinophilia and systemic symptoms (DRESS) • Acute generalised exanthematous pustulosis (AGEP) Endocrine Also reported but with unknown causal relationship, rare cases of: • gynecomastia • hypoglycemic reaction • menstrual delays of up to two weeks and dysfunctional uterine bleeding occurred in nine patients taking ibuprofen 400 mg three times a day for three days before menses Gastrointestinal • nausea • epigastric pain • heartburn • diarrhea • abdominal distress • nausea and vomiting • indigestion (dyspepsia) • constipation • abdominal cramps and pain • gastrointestinal tract fullness (bloating or • gastric or duodenal ulcer with bleeding and/or perforation • gastrointestinal hemorrhage • melena • hepatitis • jaundice • abnormal liver function (SGOT, APO-IBUPROFEN and APO-IBUPROFEN CAPLET (Ibuprofen tablets) Page 19 of 48 Adverse Effect Common (>1% but <10%) Less Common (<1%) Incidence 3-9% Incidence 1-3% flatulence) serum bilirubin and alkaline phosphatase) • pancreatitis • oral discomfort (local burning, sensation, irritation) The generally modest elevations of serum transaminase activity that has been observed are usually without clinical sequelae but severe, potentially fatal toxic hepatitis can occur.
g. prupura, epistaxis, hematuria, menorrhagia) • auto-immune hematological anemia occurred in one patient taking 400 mg of ibuprofen three times a day for ten days • fatal aplastic anemia was reported in one patient who took 600 mg per day for eight months • bone marrow toxicity • eosinophilia Metabolic • decreased appetite • edema • fluid retention.
Fluid retention generally responds promptly to drug discontinuation. Renal Also reported but with unknown causal relationship: • decreased creatinine clearance • polyuria • azotemia • nephritis • nephrotic syndrome • renal failure Like other non-steroidal anti-inflammatory agents, ibuprofen inhibits renal prostaglandin synthesis that may decrease renal function and cause sodium retention.
Renal blood flow glomerular filtration rate decreased in patients APO-IBUPROFEN and APO-IBUPROFEN CAPLET (Ibuprofen tablets) Page 20 of 48 Adverse Effect Common (>1% but <10%) Less Common (<1%) Incidence 3-9% Incidence 1-3% with mild impairment of renal functions who took 1200 mg/day of ibuprofen for one week.
• Renal papillary necrosis has been reported. A number of factors appear to increase the risk of renal toxicity (See 7 WARNINGS AND PRECAUTIONS) Special Senses • tinnitus • asthenia • amblyopia (blurred and/or diminished vision, scotomata and/or changes in colour vision) Any patient with eye complaints during ibuprofen therapy should have an ophthalmological examination Also reported but with unknown causal […]