Advel

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) used for its analgesic, antipyretic, and anti-inflammatory effects. Approved indications include:

• Pain management: Relief of mild to moderate pain from conditions such as headache, dental pain, musculoskeletal pain, postoperative pain, and primary dysmenorrhea (menstrual cramps).
• Inflammatory disorders: Treatment of rheumatoid arthritis, osteoarthritis, juvenile idiopathic arthritis, ankylosing spondylitis, and other inflammatory musculoskeletal conditions.
• Fever: Reduction of fever in adults and children.
• Other uses: Closure of patent ductus arteriosus (PDA) in neonates (specific intravenous formulations).

Off-label uses: Management of acute gout attacks (often as adjunct therapy).

Adults:

• Pain and fever: 200–400 mg orally every 4 to 6 hours as needed. Do not exceed 1200 mg per day when used over the counter; under medical supervision, doses up to 3200 mg per day divided into 3–4 doses may be used for inflammatory conditions.
• Arthritis and inflammatory conditions: 1200 to 3200 mg daily in divided doses.

Children (≥6 months):

• Dose based on weight: 5 to 10 mg/kg per dose every 6 to 8 hours as needed. Maximum daily dose should not exceed 40 mg/kg.

Elderly:

• Use the lowest effective dose for the shortest duration to reduce adverse effect risk. Monitor renal and cardiovascular status regularly.

Renal Impairment:

• Use cautiously in mild to moderate renal impairment; avoid in severe impairment (eGFR <30 mL/min).

Hepatic Impairment:

• Use with caution in mild to moderate hepatic impairment. Avoid in severe hepatic dysfunction.

Administration:

• Oral administration with or after food or milk to reduce gastrointestinal irritation.
• Multiple formulations available: tablets, capsules, suspensions, topical gels.
• Avoid concurrent use with other NSAIDs or aspirin unless prescribed.

Duration:

• Use the shortest duration possible, especially in chronic conditions.

Ibuprofen inhibits the cyclooxygenase enzymes COX-1 and COX-2, which are involved in converting arachidonic acid to prostaglandins. Prostaglandins mediate pain, inflammation, and fever. By blocking prostaglandin synthesis, ibuprofen reduces inflammation, pain sensation, and body temperature. The inhibition of COX-1 also leads to reduced platelet aggregation and can contribute to gastrointestinal mucosal damage.

• Absorption: Rapid and nearly complete after oral administration; peak plasma concentrations occur within 1 to 2 hours.
• Bioavailability: Approximately 80–100%.
• Distribution: Highly protein-bound (~99%), primarily to albumin.
• Metabolism: Extensively metabolized in the liver by CYP2C9 into inactive metabolites.
• Half-life: About 2 hours in healthy adults.
• Excretion: Primarily eliminated via the kidneys as metabolites; less than 1% excreted unchanged.

• Pregnancy:
• Category C during the first and second trimesters.
• Category D during the third trimester due to risks of premature closure of the fetal ductus arteriosus and other fetal complications. Use is contraindicated in late pregnancy.
• Lactation:
• Ibuprofen is excreted in breast milk in very low amounts and is considered compatible with breastfeeding. However, caution is advised.

• Primary Class: Nonsteroidal Anti-Inflammatory Drug (NSAID)
• Subclass: Propionic acid derivative

• Known hypersensitivity to ibuprofen or other NSAIDs.
• History of asthma, urticaria, or allergic-type reactions triggered by aspirin or other NSAIDs.
• Active or recurrent gastrointestinal bleeding or peptic ulcer disease.
• Severe renal or hepatic impairment.
• Third trimester of pregnancy.
• Concurrent use of other NSAIDs (except low-dose aspirin for cardioprotection).

• Gastrointestinal: Increased risk of serious GI bleeding, ulceration, and perforation; more common in elderly or patients with history of ulcers or on corticosteroids, anticoagulants, or SSRIs.
• Cardiovascular: May increase risk of myocardial infarction, stroke, and hypertension, particularly with prolonged use or in patients with existing cardiovascular disease.
• Renal: Can cause renal impairment or failure; monitor kidney function, especially in at-risk populations.
• Hypersensitivity: Anaphylaxis and serious skin reactions (e.g., Stevens-Johnson syndrome) may occur.
• Hepatic: Monitor liver function during prolonged therapy.
• Bleeding: Impaired platelet function may increase bleeding risk; use cautiously with anticoagulants.

Common Adverse Effects:

• Gastrointestinal: Dyspepsia, nausea, abdominal pain, diarrhea.
• Central Nervous System: Headache, dizziness, fatigue.
• Dermatologic: Rash, pruritus.

Serious and Rare Adverse Effects:

• Gastrointestinal bleeding and ulcers.
• Anaphylaxis and severe allergic reactions.
• Renal impairment or failure.
• Elevated liver enzymes or hepatitis.
• Cardiovascular events including myocardial infarction and stroke.
• Severe skin reactions such as Stevens-Johnson syndrome.

Adverse effects may occur shortly after initiation or with long-term use.

• Anticoagulants (e.g., warfarin): Increased risk of bleeding.
• Other NSAIDs or corticosteroids: Additive risk of GI toxicity.
• Antihypertensive agents (ACE inhibitors, ARBs, diuretics): May reduce effectiveness and increase risk of renal dysfunction.
• Lithium: Possible increase in lithium toxicity.
• Methotrexate: May increase methotrexate toxicity.
• CYP2C9 inhibitors or inducers: Can alter ibuprofen metabolism.
• Alcohol: Combined use increases risk of GI bleeding.

• Guidelines emphasize using the lowest effective dose for the shortest possible duration to minimize cardiovascular, gastrointestinal, and renal risks.
• The FDA and other agencies have issued warnings on increased cardiovascular and GI risks associated with NSAIDs.
• Strong recommendation to avoid NSAIDs in the third trimester of pregnancy.
• Recent clinical guidance stresses individualized patient risk assessment prior to NSAID use and regular monitoring during long-term therapy.

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F).
• Protect from moisture and light.
• Keep in the original container with the lid tightly closed.
• Do not freeze.
• Keep out of reach of children.