Ibuprofen

Ibuprofen is Non- Steroidal Ant inflammatory Drugs belonging to Analgesic and Anti inflammatory agents.

Ibuprofen is used in the Management of inflammatory diseases and rheumatoid disorders, mild to moderate pain, fever, dysmenorrhea, and osteoarthritis . It is also used to treat Abnormal uterine bleeding, nonacute; Gout, treatment (acute flares); Pericarditis, acute or recurrent

Ibuprofen is Rapidly absorbed from the gastrointestinal tract; partially into the skin. Food intake decreases absorption rate. Bioavailability: 80%.)and Enters breast milk. Volume of distribution: 0.12 L/kg (oral). Plasma protein binding: >99%.

and get Metabolized in the liver via oxidation.

and get excreted Mainly via urine (45-80% as metabolites, approx 1% as unchanged drug, 14% as conjugated); faeces. Elimination half-life: Approx 2 hours (oral); 2.22-2.44 hours (IV).

The common side effects of Ibuprofen includes hyperkalaemia, drowsiness, dizziness, blurred or diminished vision, Scotoma, changes in colour vision; photosensitivity (topical); renal papillary necrosis (prolonged use), mask symptoms of infection, Na and fluid retention, oedema, risk for impairment of female fertility

The onset of action of Ibuprofen Oral: Analgesic: Within 30 to 60 minutes,

The Duration of action of Ibuprofen was within 6-8 hours.

The Tmax of Ibuprofen was found within 1-2 hours.

The Cmax of Ibuprofen was within 41.47 and 31.88 μg/mL

Ibuprofen is available in Tablet, Capsules and oral suspension.

Ibuprofen is available in India, Germany, Canada, France, USA.

Ibuprofen is a non-selective COX inhibitor and hence, it inhibits the activity of both COX-1 and COX-2. The inhibition of COX-2 activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration.

Ibuprofen is available in the form of tablets, capsules and oral suspension.

Ibuprofen is used in the Management of inflammatory diseases and rheumatoid disorders, mild to moderate pain, fever, dysmenorrhea, and osteoarthritis . It is also used to treat Abnormal uterine bleeding, nonacute; Gout, treatment (acute flares); Pericarditis, acute or recurrent.

Ibuprofen, an NSAID, has analgesic, anti-inflammatory and antipyretic properties. It inhibits cyclooxygenase-1 and 2 thereby, reducing the production of prostaglandin precursors.

Ibuprofen is approved for use in the following clinical indications

Oral: Management of inflammatory diseases and rheumatoid disorders, mild to moderate pain, fever, dysmenorrhea, and osteoarthritis

Injection : Management of mild to moderate pain and management of moderate to severe pain as an adjunct to opioid analgesics in adults and pediatric patients ≥3 months of age; reduction of fever in adults and pediatric patients ≥3 months of age.

Patent ductus arteriosus: To close a clinically significant patent ductus arteriosus in premature infants weighing between 500 and 1,500 g who are no more than 32 weeks of gestational age when usual medical management (eg, diuretics, fluid restriction, respiratory support) is ineffective.

• Although not approved there have been certain off labelled uses documented for Ibuprofen which includes:

Abnormal uterine bleeding, nonacute (alternative agent) (off-label use): Note: Not indicated for management of acute abnormal bleeding (ie, excessively heavy or prolonged bleeding that requires urgent evaluation). Alternative for patients who cannot or choose not to use hormonal therapies. Dosing based on limited data and expert opinion.

Oral: 600 mg 2 to 4 times daily. Begin at menses onset and continue for 2 to 3 days or until cessation of bleeding.

Anti-inflammatory (eg, for arthritis associated with rheumatic disease):

Oral: 400 to 800 mg every 6 to 8 hours; maximum dose: 3.2 g/day. Some experts generally recommend a maximum dose of 2.4 g/day for chronic use, except during a disease flare when up to 3.2 g/day may be considered for several weeks until flare resolves

Dysmenorrhea:

Oral: Initial: 400 mg every 4 hours as needed or 600 to 800 mg every 6 to 8 hours as needed; maximum dose: 3.2 g/day. Begin at menses onset or 1 to 2 days prior to onset of menses for severe symptoms; usual duration: 1 to 5 days

Fever (alternative agent):

IV, Oral: 200 to 400 mg every 4 to 6 hours as needed; if fever persists, may titrate up to 600 to 800 mg every 6 hours as needed; maximum dose: 3.2 g/day

OTC labeling (patient-guided therapy): Oral: 200 mg every 4 to 6 hours as needed; if no relief, may increase to 400 mg every 4 to 6 hours as needed; maximum dose: 1.2 g/day. Use for >3 days is not recommended unless directed by health care provider.

Gout, treatment (acute flares) (off-label use):

Note: Some experts reserve use for patients who are not candidates for intra-articular glucocorticoids or when intra-articular glucocorticoid administration is not feasible

Oral: Initial: 800 mg every 8 hours within 24 to 48 hours of flare onset; reduce dose as symptoms improve; discontinue 2 to 3 days after resolution of clinical signs; usual duration: 5 to 7 days

Migraine, acute treatment:

Note: Limit use to ≤14 days per month to avoid medication-overuse headache. For use as monotherapy in mild to moderate attacks not associated with vomiting or severe nausea; may be used in combination with triptans for severe migraine. Administration early in the course of a migraine attack, at the first sign of pain, may improve response to treatment .

Oral: 400 to 600 mg once.

OTC labeling (patient-guided therapy): Oral: 400 mg at onset of symptoms.

Pain (monotherapy or as an adjunctive agent):

IV, Oral: 200 to 400 mg every 4 to 6 hours as needed or 600 to 800 mg every 6 to 8 hours as needed; maximum dose: 3.2 g/day . For postoperative pain, doses may be scheduled initially. Some experts suggest a usual maximum of 2.4 g/day for chronic use due to increased adverse effects with higher doses.

OTC labeling (patient-guided therapy): Oral: 200 mg every 4 to 6 hours as needed; if no relief, may increase to 400 mg every 4 to 6 hours as needed; maximum dose: 1.2 g/day. Use for >10 days is not recommended unless directed by health care provider.

Pericarditis, acute or recurrent (off-label use):

Note: In patients with an indication for aspirin (eg, coronary artery disease), aspirin is generally preferred over other nonsteroidal anti-inflammatory drugs (NSAIDs). Avoid non-aspirin NSAIDs in patients with pericarditis secondary to acute myocardial infarction given lack of benefit and potential harm.

Oral: Initial: 600 to 800 mg every 8 hours or 600 mg every 6 hours until resolution of symptoms for at least 24 hours and normalization of inflammatory biomarkers (eg, C-reactive protein) if monitored; initial therapy typically lasts for ≥1 to 2 weeks. Gradually taper over several weeks by decreasing each dose by 200 to 400 mg every 1 to 2 weeks; during taper, ensure patient remains asymptomatic and inflammatory biomarkers remain normal (if monitored). Use in combination with colchicine. In patients at risk of NSAID-related GI toxicity, prophylaxis (generally with a proton pump inhibitor) is recommended.

Ibuprofen is available in the dosage strength of

Tablet

• 100mg
• 200mg
• 500mg
• 400mg
• 600mg
• 800mg
• 200mg
• 100mg/5mL
• 40mg/mL

Capsule

Oral suspension

Ibuprofen is available in the form of Tablets, capsules and oral suspension.

• Dosage Adjustment in Kidney Patient

eGFR 30 to <60 mL/minute/1.73 m²: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.

eGFR <30 mL/minute/1.73 m²: Avoid use.

Hypersensitivity to ibuprofen; history of hypersensitivity reaction (e.g. bronchospasm, asthma, urticaria, angioedema, rhinitis) to aspirin or other NSAIDs. History of gastrointestinal bleeding, perforation or ulceration related to NSAID therapy; active or history of recurrent peptic ulcer or gastrointestinal haemorrhage (≥2 distinct episodes of proven ulceration or bleeding); conditions involving an increased tendency to bleeding; application on broken or damaged skin (topical). Ibuprofen lysine: Proven or suspected infection that is left untreated; congenital heart disease whom patency of PDA is necessary for satisfactory pulmonary or systemic blood flow (e.g. pulmonary artesia, severe tetralogy of Fallot, severe coarctation of the aorta); thrombocytopenia, coagulation defects, confirmed or suspected necrotising enterocolitis. Severe heart failure (New York Heart Association Class IV). Patients undergoing CABG surgery. Severe renal and hepatic impairment. Pregnancy (3rd trimester).

Concerns related to adverse effects:

• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Hyperkalemia: Nonsteroidal anti-inflammatory drug (NSAID) use may increase the risk of hyperkalemia, particularly in patients ≥65 years of age, in patients with diabetes or renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE inhibitors). Monitor potassium closely.

• Ophthalmic events: Blurred/diminished vision, Scotoma, and changes in color vision have been reported. Discontinue therapy and refer for ophthalmologic evaluation if symptoms occur. Periodically evaluate vision in all patients receiving long-term therapy.

Ibuprofen may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Rate and extent of absorption may be reduced when taken with food or milk. Increased risk of gastrointestinal bleeding with alcohol.

• Common Adverse effects:

Hyperkaliemia, drowsiness, dizziness, blurred or diminished vision, Scotoma, changes in colour vision; photosensitivity (topical); renal papillary necrosis (prolonged use), mask symptoms of infection, Na and fluid retention, oedema, risk for impairment of female fertility

• Less Common Adverse effects:

Nausea, vomiting, abdominal pain, flatulence, diarrhea, dyspepsia, constipation, melaena, hematemesis.

• Rare Adverse effects

Severe hepatic reactions (e.g. fulminant hepatitis, liver necrosis, hepatic failure). Very rarely, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis (AGEP), drug eosinophilia and systemic symptoms (DRESS), multiorgan hypersensitivity reactions.

May increase risk of ulceration or bleeding with other NSAIDs, oral corticosteroid, anticoagulants (e.g. warfarin), anti-platelet (e.g. aspirin), SSRIs. May reduce the effect of antihypertensives (e.g. ACE inhibitors, angiotensin II receptor antagonist, β blockers) and diuretics. May increase the toxicity and plasma concentration of cardiac glycosides. Decreased excretion of lithium, methotrexate, aminoglycosides. Increased risk of nephrotoxicity with ciclosporin and tacrolimus. May increase the risk of convulsions with quinolone antibiotics. May potentiate the effects of sulfonylureas. Increased risk of haematological toxicity with zidovudine. Concomitant use with CYP2C9 inhibitors (e.g. fluconazole, vorizonazole) may increase plasma concentration of ibuprofen.

The common side effects of Ibuprofen include the following :

Hyperkaliemia, drowsiness, dizziness, blurred or diminished vision, Scotoma, changes in color vision; photosensitivity (topical); renal papillary necrosis (prolonged use), mask symptoms of infection, Na and fluid retention, oedema, risk for impairment of female fertility.

Symptoms: Headache, drowsiness, dizziness, loss of consciousness, convulsions, disorientation, excitation, fainting, tinnitus, nausea, vomiting, abdominal pain, diarrhoea, gastrointestinal bleeding, nystagmus, hypothermia, hypotension, bradycardia, tachycardia, apnoea, CNS and respiratory depression, acute renal failure, liver damage, lethargy, metabolic acidosis, prolonged prothrombin time or INR, coma.

Management: Supportive and symptomatic treatment. Consider giving activated charcoal, inducing emesis with ipecac syrup, or performing gastric lavage within 1 hour of ingestion. Ensure good urine output. Monitor renal and liver function. Administer IV diazepam for frequent or prolonged convulsions.

• Pharmacodynamic

Ibuprofen is a non-selective COX inhibitor and hence, it inhibits the activity of both COX-1 and COX-2. The inhibition of COX-2 activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration.

• Pharmacokinetics

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
2. https://reference.medscape.com/drug/colestid-Ibuprofen -342452
3. https://go.drugbank.com/drugs/DB00375
4. https://www.sciencedirect.com/topics/medicine-and-dentistry/Ibuprofen
5. https://europepmc.org/article/med/6988203