Ibuprofen

1. Drug Name

• Generic Name: Ibuprofen

• Brand Names: Advil, Motrin, Nurofen, Brufen, and Ibugesic

2. Drug Classification

• Class: Nonsteroidal Anti-inflammatory Drug (NSAID)

• Subclass: Propionic acid derivative

3. Mechanism of Action

• Ibuprofen works primarily by inhibiting cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2.

• By blocking COX enzymes, ibuprofen reduces the synthesis of prostaglandins, which are lipid compounds involved in the generation of pain, inflammation, and fever.

• This COX inhibition mechanism also leads to ibuprofen’s antipyretic (fever-reducing), analgesic (pain-relieving), and anti-inflammatory properties.

• At a cellular level, by decreasing prostaglandin E2 production, it lowers the sensitivity of pain receptors and decreases inflammatory responses.

4. Pharmacokinetics

• Absorption: Rapidly absorbed from the gastrointestinal tract with a bioavailability of approximately 80-90%. Peak plasma levels are typically reached within 1-2 hours after oral administration.

• Distribution: Ibuprofen has a volume of distribution (Vd) of around 0.1-0.2 L/kg and exhibits high protein binding (90-99%), primarily to albumin.

• Metabolism: Primarily metabolized in the liver by the CYP2C9 enzyme system. It undergoes hydroxylation and carboxylation to form inactive metabolites.

• Excretion: The half-life (t½) of ibuprofen is around 2-4 hours. It is eliminated via renal excretion, with about 90% excreted as metabolites and 10% unchanged.

• Special Considerations: Dosing adjustments may be necessary in patients with liver dysfunction, as metabolism could be compromised, and in older adults, who may experience prolonged drug levels due to decreased renal clearance.

5. Indications

• Primary Indications:

  • Pain relief in conditions like headaches, toothache, muscle pain, and dysmenorrhea.

  • Anti-inflammatory effects in osteoarthritis and rheumatoid arthritis.

  • Fever reduction in adults and children.

• Off-Label Uses:

  • Gout (acute attacks) as a short-term anti-inflammatory.

  • Management of mild to moderate pain post-surgery or injury.

• Specific Populations:

  • Effective in both adults and children over six months for pain and fever; caution is advised in the elderly and in patients with renal or hepatic impairments.

6. Dosage and Administration

• Adults:

  • Pain relief: 200-400 mg orally every 4-6 hours as needed. Maximum daily dose is generally 3,200 mg, although lower doses are often recommended for safety.

• Pediatric:

  • Dosage varies based on age and weight (typically 5-10 mg/kg/dose every 6-8 hours, not exceeding 40 mg/kg/day).

• Route: Primarily oral; also available in topical, intravenous, and rectal formulations.

• Dosing Adjustments:

  • Renal impairment: Caution with severe impairment; use lower doses.

  • Hepatic impairment: Avoid high doses; periodic monitoring recommended.

• Maximum Safe Dose: For chronic use, often limited to 2,400 mg daily to reduce gastrointestinal and cardiovascular risks.

7. Contraindications

• Absolute Contraindications:

  • Known hypersensitivity to ibuprofen or other NSAIDs.

  • History of asthma, urticaria, or allergic-type reactions after taking NSAIDs.

  • Active gastrointestinal bleeding, peptic ulcer disease, or severe gastrointestinal disorders.

  • Severe heart failure, renal failure, or hepatic impairment.

• Relative Contraindications:

  • Caution in patients with cardiovascular disease, mild renal/hepatic dysfunction, or a history of gastrointestinal bleeding.

8. Warnings and Precautions

• Black Box Warning:

  • Increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke.

  • Increased risk of gastrointestinal bleeding, ulceration, and perforation.

• Special Warnings:

  • Pregnancy: Contraindicated in the third trimester due to risk of premature closure of the ductus arteriosus.

  • Lactation: Generally considered safe in small doses, but prolonged use should be avoided.

• Monitoring Parameters:

  • Renal and hepatic function in long-term use, especially in elderly patients.

  • Complete blood count and liver enzymes periodically if used chronically.

9. Adverse Effects

• Common Adverse Effects (≥10%):

  • Gastrointestinal upset (nausea, dyspepsia, abdominal pain).

  • Headache, dizziness, and drowsiness.

• Less Common but Clinically Significant:

  • Fluid retention, hypertension.

  • Rash or other allergic skin reactions.

• Rare/Serious Adverse Reactions:

  • Anaphylactic reactions.

  • Severe skin reactions like Stevens-Johnson Syndrome and toxic epidermal necrolysis.

  • Acute kidney injury, particularly in cases of dehydration.

10. Drug Interactions

• Major Drug Interactions:

  • Anticoagulants (e.g., warfarin): Increased risk of bleeding.

  • Antihypertensives (e.g., ACE inhibitors, diuretics): May reduce antihypertensive efficacy.

  • Methotrexate: Increased toxicity due to decreased renal clearance.

• Food-Drug Interactions:

  • Food may delay absorption, but it doesn’t significantly affect overall bioavailability. Taking ibuprofen with food can reduce gastrointestinal irritation.

• Interactions with Lab Tests:

  • Can cause false elevations in liver enzyme levels.

11. Clinical Pharmacology

• Ibuprofen exhibits analgesic, anti-inflammatory, and antipyretic effects due to inhibition of COX enzymes, reducing prostaglandin synthesis.

• Unlike some other NSAIDs, ibuprofen has a relatively shorter half-life and is considered a weaker COX-1 inhibitor, making it somewhat safer for gastrointestinal protection, especially at lower doses.

12. Special Populations

• Pregnancy: Category C (1st and 2nd trimesters), Category D (3rd trimester). Avoid use during the third trimester due to risks to fetal cardiovascular development.

• Lactation: Generally compatible with breastfeeding, but use the lowest effective dose and avoid prolonged use.

• Geriatrics: Increased risk of gastrointestinal and renal side effects; use lower doses and monitor renal function.

• Renal/Hepatic Dysfunction: Caution advised; dose adjustments and monitoring are necessary.

13. Therapeutic Uses

• First-Line Therapy: For mild to moderate pain, fever, and inflammatory conditions.

• Second-Line or Adjunctive Therapy: Can be used alongside other agents for inflammatory arthritic conditions or in combination with paracetamol for multimodal analgesia.

14. Monitoring and Follow-Up

• Recommended Lab Tests: Baseline renal function and liver function tests for prolonged use.

• Patient-Reported Symptom Checklists: Gastrointestinal symptoms, signs of bleeding, and changes in urine output.

• Monitoring of Therapeutic and Toxic Levels: Monitor symptoms and adjust doses accordingly, particularly in patients with comorbidities.

15. Overdose Management

• Symptoms of Overdose: Nausea, vomiting, abdominal pain, drowsiness, headache, nystagmus, and, in severe cases, metabolic acidosis, renal failure, or respiratory depression.

• Treatment Protocols:

  • Activated charcoal within 1-2 hours of overdose if ingestion is recent.

  • IV fluids, acid-base management, and symptomatic care.

  • No specific antidote; dialysis is ineffective due to high protein binding.

16. Patient Counseling Information

• Advise patients to take ibuprofen with food to minimize gastrointestinal upset.

• Instruct them to avoid alcohol to reduce the risk of gastrointestinal side effects.

• Inform about potential signs of adverse effects, such as gastrointestinal bleeding, dizziness, or skin rashes, which warrant immediate medical attention.