Ibuprofen - Drug Monograph

Introduction

Ibuprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID) belonging to the propionic acid derivative class. First introduced in 1969, it has become one of the most commonly prescribed and utilized medications worldwide for its analgesic, anti-inflammatory, and antipyretic properties. As a non-selective cyclooxygenase inhibitor, it provides effective relief for various pain and inflammatory conditions while maintaining a generally favorable safety profile when used appropriately.

Mechanism of Action

Ibuprofen exerts its therapeutic effects through reversible inhibition of cyclooxygenase (COX) enzymes, primarily COX-1 and COX-2. These enzymes catalyze the conversion of arachidonic acid to prostaglandin H2, the precursor for various prostaglandins, thromboxanes, and prostacyclins. By inhibiting prostaglandin synthesis, ibuprofen reduces:

• Inflammation: Decreased production of prostaglandins involved in the inflammatory response
• Pain: Lowered sensitization of pain receptors to chemical and mechanical stimuli
• Fever: Reduction of prostaglandin E2 in the hypothalamus, normalizing the elevated temperature set-point

The drug's antiplatelet effects result from inhibition of thromboxane A2 synthesis, though this effect is reversible and shorter-lasting than with aspirin.

Indications

• Mild to moderate pain management
• Primary dysmenorrhea
• Osteoarthritis and rheumatoid arthritis
• Fever reduction

• Migraine headaches
• Gout attacks
• Inflammatory musculoskeletal disorders
• Postoperative pain management

Dosage and Administration

• Analgesia/Antipyretic: 200-400 mg every 4-6 hours (max 1200 mg/day)
• Anti-inflammatory: 400-800 mg three to four times daily (max 3200 mg/day)

• Fever: 5-10 mg/kg every 6-8 hours (max 40 mg/kg/day)
• Juvenile idiopathic arthritis: 30-40 mg/kg/day in 3-4 divided doses

• Renal impairment: Avoid in advanced renal disease (CrCl <30 mL/min)
• Hepatic impairment: Use lowest effective dose with close monitoring
• Geriatric patients: Start with lower doses due to increased sensitivity

• Take with food or milk to minimize gastrointestinal upset
• Swallow tablets whole with adequate fluid
• Do not crush or chew extended-release formulations

Pharmacokinetics

Contraindications

• Hypersensitivity to ibuprofen or other NSAIDs
• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
• Peri-operative pain in coronary artery bypass graft (CABG) surgery
• Third trimester of pregnancy
• Active peptic ulcer disease or gastrointestinal bleeding
• Severe renal impairment (CrCl <30 mL/min)
• Severe hepatic impairment (Child-Pugh Class C)

Warnings and Precautions

• Increased risk of serious cardiovascular thrombotic events, including MI and stroke
• Risk may increase with duration of use
• Patients with cardiovascular disease or risk factors may be at greater risk

• Serious GI adverse events including bleeding, ulceration, and perforation
• Risk factors: advanced age, history of ulcer disease, concomitant anticoagulant use, prolonged use, higher doses

• May cause renal papillary necrosis and other renal injury
• Risk increased in dehydration, heart failure, hepatic cirrhosis, diuretic use

• May cause severe hepatic reactions including liver failure
• Monitor for symptoms of hepatic dysfunction

Drug Interactions

• Anticoagulants (warfarin): Increased bleeding risk
• Other NSAIDs/aspirin: Increased GI toxicity
• ACE inhibitors/ARBs: Reduced antihypertensive effect
• Diuretics: Reduced diuretic effectiveness
• Lithium: Increased lithium levels
• Methotrexate: Increased methotrexate toxicity
• SSRIs/SNRIs: Increased bleeding risk
• Cyclosporine: Increased nephrotoxicity

Adverse Effects

• Dyspepsia, nausea, abdominal pain
• Headache, dizziness
• Rash
• Edema

• GI bleeding/perforation
• Cardiovascular thrombotic events
• Renal impairment/failure
• Hepatic injury
• Severe skin reactions (SJS/TEN)
• Anaphylactic reactions
• Hematologic toxicity (anemia, neutropenia)

Monitoring Parameters

• Complete medical history including GI, cardiovascular, and renal status
• Blood pressure
• Renal function tests (BUN, creatinine)
• Liver function tests
• CBC if long-term use anticipated

• Signs/symptoms of GI bleeding
• Blood pressure monitoring
• Renal function with long-term use
• Hepatic function with symptoms
• Signs of fluid retention
• Therapeutic efficacy and pain control

Patient Education

• Take with food or milk to reduce stomach upset
• Do not exceed recommended dosage
• Report any signs of GI bleeding (black stools, abdominal pain)
• Monitor for signs of allergic reactions
• Avoid concurrent use of other NSAIDs
• Be aware of potential cardiovascular and renal risks
• Do not use during third trimester of pregnancy
• Store at room temperature away from moisture
• Seek immediate medical attention for chest pain, shortness of breath, weakness, or slurred speech

References

1. Drugs.com. Ibuprofen Professional Monograph. 2023 2. UpToDate. Ibuprofen: Drug Information. 2023 3. American Society of Health-System Pharmacists. AHFS Drug Information. 2023 4. FDA Prescribing Information for Advil/Motrin. 2022 5. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th edition 6. McEvoy GK, et al. American Hospital Formulary Service Drug Information. 2023 7. Osteoarthritis Research Society International guidelines for non-surgical management of knee osteoarthritis. 2019 8. American College of Rheumatology guidelines for management of osteoarthritis. 2019