Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2004 Publisher: Gebro Pharma GmbH, A-6391, Fieberbrunn, Austria
Dexibuprofen must not be administered in the following cases:
Care is recommended in conditions that predispose patients to the gastrointestinal adverse effects of NSAIDs such as dexibuprofen, including existing gastrointestinal disorders, previous gastric or duodenal ulcer, ulcerative colitis, Crohn’s disease and alcoholism.
These patients should be closely monitored for digestive disturbances, especially gastrointestinal bleeding, when taking dexibuprofen or any other NSAID.
Gastrointestinal bleeding or ulceration/perforation have in general more serious consequences in the elderly. They can occur at any time during treatment with or without warning symptoms or a previous history of serious gastrointestinal events.
In the rare instances where gastrointestinal bleeding or ulceration occurs in patients receiving dexibuprofen, treatment should be immediately discontinued (see 4.3. Contraindications).
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, can also occur without earlier exposure to the drug.
In the treatment of patients with heart failure, hypertension, renal or hepatic disease, especially during concomitant diuretic treatment, the risk of fluid retention and a deterioration in renal function must be taken into account. If used in these patients, the dose of dexibuprofen should be kept as low as possible and renal function should be regularly monitored.
Caution must be exercised in the treatment of elderly patients, who generally have a greater tendency to experience side effects to NSAIDs.
Dexibuprofen should only be given with care to patients with systemic lupus erythematosus and mixed connective tissue disease, because such patients may be predisposed to NSAID-induced CNS and renal side effects.
Caution is required in patients suffering from, or with a previous history of, bronchial asthma since NSAIDs can cause bronchospasm in such patients (see 4.3 Contraindications).
NSAIDs may mask the symptoms of infections.
As with all NSAIDs, dexibuprofen can increase plasma urea nitrogen and creatinine. As with other inhibitors of NSAIDs, dexibuprofen can be associated with adverse effects on the renal system, which can lead to glomerular nephritis, interstitial nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure (see 4.2. Posology, 4.3. Contraindications and 4.5 Interactions).
As with other NSAIDs, dexibuprofen can cause transient small increases in some liver parameters, and also significant increases in SGOT and SGPT. In case of a relevant increase in such parameters, therapy must be discontinued (see 4.2. Posology and 4.3. Contraindications).
In common with other NSAIDs dexibuprofen may reversibly inhibit platelet aggregation and function and prolong bleeding time. Caution should be exercised when dexibuprofen is given concurrently with oral anticoagulants (see section 4.5).
Patients receiving long-term treatment with dexibuprofen should be monitored as a precautionary measure (renal, hepatic functions and haematologic function/blood counts).
During long-term, high dose, off-label treatment with analgesic drugs, headaches can occur which must not be treated with higher doses of the medicinal product.
In general the habitual use of analgesics, especially the combination of different analgesic drug substances, can lead to lasting renal lesions with the risk of renal failure (analgesic nephropathy). Thus combinations with racemic ibuprofen or other NSAIDs (including OTC products) should be avoided.
The use of dexibuprofen, as with any other drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility reversibly and is not recommended in women attempting to conceive. In women who have difficulty conceiving or who are undergoing investigation of infertility, withdrawal of Seractil should be considered.
Data of preclinical studies indicate that inhibition of platelet aggregation by low-dose acetylsalicylic acid may be impaired if ibuprofen is administrated concurrently;
this interaction could reduce the cardiovascular-protective effect. Therefore if concomitant administration of low-dose acetylsalicylic acid is indicated special precaution is required if duration of treatment exceeds short term use.
The information in this section is based upon previous experience with racemic ibuprofen and other NSAIDs.
In general, NSAIDs should be used with caution with other drugs that can increase the risk of gastrointestinal ulceration or gastrointestinal bleeding or renal impairment.
The effects of anticoagulants on bleeding time can be potentiated by NSAIDs. If concomitant treatment can not be avoidedblood coagulation tests (INR, bleeding time) should be performed during the initiation of dexibuprofen treatment and the dosage of the anticoagulant should be adjusted if necessary (see section 4.4).
If NSAIDs and methotrexate are given within 24 hours of each other plasma levels of methotrexate may increase, via a reduction in its renal clearance thus increasing the potential for methotrexate toxicity. Therefore, in patients receiving high-dose treatment with methotrexate, the concomitant use of dexibuprofen is not recommended (see section 4.4).
NSAIDs can increase the plasma levels of lithium, by reducing its renal clearance. The combination is not recommended (see section 4.4). Frequent lithium monitoring should be performed. The possibility of reducing the dose of lithium should be considered.
The concomitant use with other NSAIDs should be avoided, since simultanous administration of different NSAIDs can increase the risk of gastrointestinal ulceration and haemorrhage.
Concomitant administration of ibuprofen may impair inhibition of platelet aggregation by low-dose acetylsalicylic acid.
NSAIDs may reduce the efficacy of beta-blockers, possibly due to inhibition of the formation of vasodilatory prostaglandins.
The concomitant use of NSAIDs and ACE inhibitors or angiotensin-II receptor antagonists may be associated with an increased risk of acute renal failure, especially in patients with pre-existing impairment of renal function. When given to the elderly and/or dehydrated patients, such a combination can lead to acute renal failure by acting directly on glomerular filtration. At the beginning of the treatment, a careful monitoring of renal function is recommended.
Furthermore, chronic administration of NSAIDs can theoretically reduce the antihypertensive effect of angiotensin-II receptor antagonists, as reported with ACE inhibitors. Therefore, caution is required when using such a combination and at the start of treatment, renal function should be carefully monitored (and patients should be encouraged to maintain adequate fluid intake).
Concomitant administration with NSAIDs may increase the risk of nephrotoxicity on account of reduced synthesis of prostaglandins in the kidney. During combination treatment renal function must be closely monitored, especially in the elderly.
The risk of gastrointestinal ulceration may be increased by the concomitant administration of NSAIDs and corticosteroids.
NSAIDs can increase the plasma levels of digoxin and increase the risk of digoxin toxicity.
Ibuprofen has been reported to increase methotrexate levels. If dexibuprofen is used in combination with low doses of methotrexate, then the patient’s blood count should be monitored carefully, particularly during the first weeks of coadministration. An increased surveillance is required in the presence of even mildly impaired renal function, notably in the elderly, and renal function should be monitored to anticipate any reductions in the clearance of methotrexate.
Ibuprofen may displace phenytoin from protein-binding sites, possibly leading to increased phenytoin serum levels and toxicity. Although clinical evidence for this interaction is limited, phenytoin dosage adjustment, based on monitoring of plasma concentrations and/or observed signs of toxicity, is recommended.
Concurrent use of an NSAID and a diuretic may increase the risk of renal failure secondary to a reduction in renal blood flow.
Drugs increasing potassium plasma levels: As with other NSAIDs, concomitant treatment with drugs increasing potassium plasma levels, like potassium-sparing diuretics, ACE inhibitors, angiotensin-II receptors antagonists, immunosuppressants like cyclosporin or tacrolimus, trimethoprime, heparins, etc... may be associated with increased serum potassium levels; hence serum potassium levels should be monitored.
Dexibuprofen inhibits platelet aggregation via inhibition of platelet cyclooxygenase. Therefore, caution is required when dexibuprofen is combined with thrombolytics, ticlopidine and other antiplatelet agents, because of the risk of increased antiplatelet effect.
For dexibuprofen, no clinical data on exposed pregnancies are available. Animal studies with ibuprofen and other NSAIDs have shown reproductive toxicity (see 5.3 Preclinical Safety Data).
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/fetal development, and as the consequences of inhibiting the synthesis of prostaglandins are not fully known, dexibuprofen, like other drugs of this class, should only be administered in the first 5 months of pregnancy if clearly needed, in the lowest effective dose and as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose:
Therefore, from the beginning of the 6th month of pregnancy onward dexibuprofen is contraindicated.
The use of dexibuprofen, as with any drug substance known to inhibit cyclooxygenase/prostaglandin synthesis is not recommended in women attempting to conceive (see 4.4).
Ibuprofen is slightly excreted in human milk. Breast-feeding is possible with dexibuprofen if dosage is low and the treatment period is short.
During treatment with dexibuprofen the patient’s reaction capacity may be reduced when dizziness or fatigue appear as side effects. This should be taken into consideration when increased alertness is required, e.g. when driving or operating machinery. For a single or short term use of Dexibuprofen no special precautions are necessary.
Clinical experience has shown that the risk of undesirable effects induced by dexibuprofen is comparable to that of racemic ibuprofen. The most common adverse events are gastrointestinal in nature.
It should be noted that the adverse events listed below include those reported predominantly for racemic ibuprofen, even though in some cases the adverse event has either not yet been observed with dexibuprofen or has not yet been reported in the frequency mentioned.
Very common (>1/10): Dyspepsia, diarrhoea.
Common (>1/100, <1/10): Nausea, vomiting, abdominal pain.
Uncommon (>1/1,000, <1/100): Gastrointestinal ulcers and bleeding, ulcerative stomatitis.
Rare (>1/10,000, <1/1,000): Gastrointestinal perforation, flatulence, constipation, esophagitis, esophageal strictures. Exacerbation of diverticular disease, unspecific haemorrhagic colitis, colitis ulcerosa or Crohn’s disease.
If gastrointestinal blood loss occurs, this may cause anaemia and haematemesis.
Common: Rash.
Uncommon: Urticaria, pruritus, purpura (including allergic purpura), angiooedema, rhinitis, bronchospasm.
Rare: Anaphylactic reaction
Very rare (<1/10,000): Erythema multiforme, epidermal necrolysis, systemic lupus erythematosus, alopecia, photosensitivity reactions, severe skin reactions like Stevens-Johnson-Syndrome, acute toxic epidermal necrolysis (Lyell-Syndrome) and allergic vasculitis.
Generalized hypersensitivity reactions have not yet been reported with dexibuprofen but their occurrence cannot be excluded considering the clinical experience with racemic ibuprofen. The symptoms may include fever with rash, abdominal pain, headache, nausea and vomiting, signs of liver injury and even aseptic meningitis. In the majority of cases in which aseptic meningitis has been reported with ibuprofen, some form of underlying auto-immune disease (such as systemic lupus erythematosus or other collagen diseases) was present as a risk factor. In case of a severe generalized hypersensitivity reaction swelling of face, tongue and larynx, bronchospasm, asthma, tachycardia, hypotension and shock can occur.
Common: Fatigue or drowsiness, headache, dizziness, vertigo.
Uncommon: Insomnia, anxiety, restlessness, visual disturbances, tinnitus.
Rare: Psychotic reaction, agitation, irritability, depression, confusion or disorientation, reversible toxic amblyopia, impaired hearing.
Very rare: Aseptic meningitis (see hypersensitivity reactions).
Bleeding time may be prolonged. Rare cases of blood disorders include: Thrombocytopenia, leucopenia, granulocytopenia, pancytopenia, agranulocytosis, aplastic anemia or haemolytic anaemia.
Peripheral oedema has been reported in association with dexibuprofen treatment.
Patients with hypertension or renal impairment seem to be predisposed to fluid retention.
Hypertension or cardiac failure (especially in the elderly) may occur.
According to the experience with NSAIDs in general, interstitial nephritis, nephrotic syndrome or renal failure cannot be excluded.
Rare cases of abnormal liver function, hepatitis and jaundice have been observed with racemic ibuprofen.
In very rare cases infection related inflammation may be aggravated.
Not applicable.
© 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.
