Chemical formula: C₁₃H₁₈O₂ Molecular mass: 206.281 g/mol PubChem compound: 3672
Ibuprofen interacts in the following cases:
Concomitant administration of ibuprofen with CYP2C9 inhibitors may increase the exposure to ibuprofen (CYP2C9 substrate). In a study with voriconazole and fluconazole (CYP2C9 inhibitors) an increased S(+)-ibuprofen exposure by approximately 80 to 100% has been shown. Reduction of the ibuprofen dose should be considered when potent CYP2C9 inhibitors are administered concomitantly, particularly when high-dose ibuprofen is administered with either voriconazole or fluconazole.
Selective serotonin re-uptake inhibitors (SSRIs) and NSAIDs each entail an increased risk of bleeding, e.g. from the gastrointestinal tract. This risk is increased by combination therapy. The mechanism may possibly be linked to reduced uptake of serotonin in the platelets.
NSAIDs may potentiate the effects of sulfonylurea medications. There are rare reports of hypoglycaemia in patients on sulfonylurea medications receiving ibuprofen.
NSAIDs may increase the effect of anticoagulants such as warfarin. Experimental studies show that ibuprofen reinforces the effects of warfarin on bleeding time. NSAIDs and the dicumarol group are metabolised by the same enzyme, CYP2C9.
In co-administration of ibuprofen with antiplatelet drugs there is increased risk of gastrointestinal bleeding.
NSAIDs can exacerbate heart failure, reduce glomerular filtration and increase plasma cardiac glycoside (e.g. digoxin) levels.
NSAIDs can reduce the effect of diuretics and other antihypertensive agents.
NSAIDs can counteract the antihypertensive effect of thiazides.
NSAIDs can counteract the diuretic effect of furosemide and bumetanide, possibly through inhibition of prostaglandin synthesis.
NSAIDs counteract the antihypertensive effect of beta-adrenoceptor blocking drugs.
There is an increased risk of acute renal failure, usually reversible, in patients with renal impairment (e.g. dehydrated and/or elderly patients) when treatment with ACE inhibitors or angiotensin-II antagonists is given at the same time as NSAIDs, including selective cyclooxygenase-2 inhibitors. The combination should, therefore, be given with care to patients with renal impairment, especially elderly patients. Patients should be adequately hydrated and a check of renal function should be considered after the initiation of combination treatment and at regular intervals during treatment.
NSAIDs may reduce the excretion of aminoglycosides.
Children: Care should be taken during concomitant treatment with ibuprofen and aminoglycosides.
Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.
Concomitant treatment of ibuprofen with corticosteroids gives rise to an increased risk of gastrointestinal ulceration or bleeding.
Concomitant administration of ibuprofen and acetylsalicylic acid is not generally recommended because of the potential of increased adverse effects.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Although there are uncertainties regarding extrapolation of these data to the clinical situation, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use.
Experimental studies indicate that ibuprofen counteracts the effect of captopril on sodium excretion.
The concomitant administration of ibuprofen and colestyramine retards and reduces (by 25%) the absorption of ibuprofen. These drugs should be given at an interval of at least 2 hours.
The concomitant administration of NSAIDs and ciclosporine is thought to be capable of increasing the risk of nephrotoxicity due to decreased synthesis of prostacyclin in the kidney. Accordingly, in the event of combination treatment, renal function must be monitored closely.
Ibuprofen reduces the renal clearance of lithium, as a result of which serum lithium levels may rise. The combination should be avoided unless frequent checks of serum lithium can be carried out and a possible reduction in the dose of lithium made.
The risk of a potential interaction between an NSAID and methotrexate should also be taken into account in connection with low-dose treatment with methotrexate, especially in patients with renal impairment. Whenever combination treatment is given, renal function should be monitored. Caution should be exercised if both an NSAID and methotrexate are given within 24 hours, as the plasma levels of methotrexate can increase, resulting in increased toxicity.
A decrease in the efficacy of the medicinal product can theoretically occur due to the antiprostaglandin properties of non-steroidal anti-inflammatory drugs (NSAIDs) including acetylsalicylic acid. Limited evidence suggests that co-administration of NSAIDs on the day of prostaglandin administration does not adversely influence the effects of mifepristone or the prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medical termination of pregnancy.
An interaction with pemetrexed as there is an increased risk of its toxicity by decreased renal clearance. In patients with an impaired renal function displaying a creatinine clearance between 45-80 ml/min, this combination is to be avoided. In patients with normal renal function, a precaution for use is sufficient based on laboratory tests of the renal function.
Probenecid slows the excretion of NSAIDs, with possible increase of their plasma concentrations.
In co-administration of ibuprofen (NSAIDs) with ritonavir it is a possible increase in the concentration of NSAIDs.
Concomitant administration of NSAIDs and tacrolimus is thought to be capable of increasing the risk of nephrotoxicity due to decreased synthesis of prostacyclin in the kidney. Accordingly, in the event of combination treatment, renal function should be monitored closely.
There is evidence of an increased risk of haemarthroses and haematoma in HIV haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
Aseptic meningitis has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease.
Caution is required if ibuprofen is administered to patients suffering from, or with a previous history of, bronchial asthma, chronic rhinitis or allergic disease since ibuprofen have been reported to cause bronchospasm, urticaria or angioedema in such patients.
Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate heart failure as fluid retention and oedema have been reported in association with NSAID therapy. NSAIDs might decrease the effect of diuretics and other antihypertensive agents.
Clinical studies suggest that use of ibuprofen, particularly at a high dose (2400 mg/day) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g. ≤1200 mg/day) is associated with an increased risk of arterial thrombotic events.
Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (2400 mg/day) should be avoided.
Careful consideration should also be exercised before initiating long-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking), particularly if high doses of ibuprofen (2400 mg/day) are required.
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.
Ibuprofen can inhibit platelet aggregation, resulting in prolongation of bleeding time. Hence, careful monitoring of patients with coagulation disorders or taking anticoagulants is recommended.
Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.
Although no teratogenic effects have been demonstrated, ibuprofen should be avoided during pregnancy. The onset of labour may be delayed and the duration of labour increased.
During the 3rd trimester, ibuprofen is contraindicated as there is a risk of premature closure of foetal ductus arteriosus with possible persistent pulmonary hypertension. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child.
Ibuprofen appears in breast milk in very low concentrations but is unlikely to affect breast fed infants adversely.
It is not expected that ibuprofen oral suspension would interfere with the ability to drive or operate machinery at the recommended dose and duration of therapy.
None known.
The undesirable effects are mainly associated with the pharmacological effect of ibuprofen on prostaglandin synthesis. The most common effects are dyspepsia and diarrhoea, which are estimated to occur in about 10–30% of treated patients.
Adverse events at least possibly related to ibuprofen are displayed by MedDRA frequency convention and system organ class database. The following frequency groupings are used: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to <1/100), Rare (≥1/10000 to <1/1000), Very rare (<1/10,000) and Not known (cannot be estimated from the available data).
Uncommon: Rhinitis
Rare: Aseptic meningitis
Uncommon: Leukopenia, thrombocytopenia, agranulocytosis, neutropenia, aplastic anaemia and haemolytic anaemia
Rare: Anaphylactic reaction
Uncommon: Insomnia, anxiety
Rare: Depression, confusional state
Common: Headache, dizziness
Uncommon: Paraesthesia, somnolence
Rare: Optic neuritis
Uncommon: Visual impairment
Rare: Toxic optic neuropathy
Uncommon: Hearing impaired
Rare: Tinnitus, vertigo
Uncommon: Asthma, bronchospasm, dyspnoea
Common: Dyspepsia, diarrhoea, nausea, vomiting, abdominal pain, flatulence, constipation, melaena, haematemesis, gastrointestinal haemorrhage
Uncommon: Gastritis, duodenal ulcer, gastric ulcer, mouth ulceration, gastrointestinal perforation
Very rare: Pancreatitis
Not known: Exacerbation of Colitis and Crohn’s disease
Uncommon: Hepatitis, jaundice, abnormal hepatic function
Rare: Liver injury
Very rare: Hepatic failure
Common: Rash
Uncommon: Urticaria, pruritus, purpura, angioedema, photosensitivity reaction
Very rare: Severe forms of skin reactions (e.g. erythema multiforme, bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis)
Not known: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)
Uncommon: Nephrotoxity in various forms e.g. tubulointerstitial nephritis, nephrotic syndrome and renal failure
Common: Fatigue
Rare: Oedema
Not known: Cardiac failure, myocardial infarction
Not known: Hypertension
Cardiac disorders and vascular disorders: Oedema, hypertension and heart failure have been reported in association with NSAID treatment. Clinical studies suggest that use of ibuprofen, particularly at a high dose (2400 mg/day) may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke.
Gastrointestinal disorders: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur.
Immune system disorders: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reaction and anaphylaxis, (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or © assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and, very rarely, erythema multiforme, bullous dermatoses (including Stevens-Johnson syndrome and toxic epidermal necrolysis).
Infections and infestations: Rhinitis and aseptic meningitis (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of stiff neck, headache, nausea, vomiting, fever or disorientation.
Exacerbation of infection-related inflammations (e.g. development of necrotising fasciitis) coinciding with the use of NSAIDs has been described. If signs of an infection occur or get worse during use of Ibuprofen the patient is therefore recommended to go to a doctor without delay.
Skin and subcutaneous tissue disorders: In exceptional cases, severe skin infections and soft-tissue complications may occur during a varicella infection (see also “Infections and infestations”).
Ibuprofen can cause prolongation of bleeding time through reversible inhibition of platelet aggregation.
Deterioration of ulcerative colitis and Crohn’s disease have been reported in connection with NSAID treatment.
Very rarely, susceptible patients may experience the following side effects with ibuprofen, but these are extremely uncommon when ibuprofen is administered topically. If they occur, treatment should be discontinued:
Hypersensitivity: Hypersensitivity reactions have been reported following treatment with ibuprofen. These may consist of (a) non-specific allergic reaction and anaphylaxis (b) respiratory tract reactivity comprising of asthma, aggravated asthma, brochospasm or dyspnoea, or © assorted skin disorders, including rashes of various types, pruritis, urticaria, purpura, angioedema and less commonly, bullous dermatoses (including epidermal necrolysis and erythema multiforme).
Gastro-intestinal: Side effects such as abdominal pain and dyspepsia have been reported.
Renal: Renal impairment can occur in patients with a history of kidney problems.
Photosensitivity reactions: frequency unknown.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
