Summary of Product Characteristics (SmPC) - Fenbid Biphasic 400 mg capsules
1 NAME OF THE MEDICINAL PRODUCT
Fenbid Biphasic 400 mg capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 400 mg of Ibuprofen Ph. Eur.
3 PHARMACEUTICAL FORM
Oral capsules with immediate and sustained release components.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Fenbid is indicated for its analgesic and anti-inflammatory effects in the treatment of rheumatoid arthritis (including juvenile rheumatoid arthritis or Still’s disease), ankylosing spondylitis, osteoarthritis and other non-rheumatoid (seronegative) arthropathies.
It may also be used in non-articular rheumatic conditions and soft tissue injuries, including low back pain, capsulitis of the shoulder, bursitis, tendinitis, tenosynovitis, dysmenorrhoea, dental and postoperative pain, sprains and strains.
4.2 Posology and method of administration
Posology
Adults: 1 capsule twice daily. The dose may be increased to two capsules twice daily if necessary. The first should be taken in the morning and the second 8-12 hours later. The capsules should be taken with or after food.
Fenbid is not recommended for children under 12 years of age.
Patients should be instructed not to chew or suck the capsules as this destroys the sustained release properties. Providing this is ensured, the contents of a capsule may be sprinkled onto a spoonful of soft food, yoghurt, or similar substance, for patients who experience difficulty in swallowing the capsule.
Elderly Patients: It would appear that advanced age has minimal influence on the pharmacokinetics of ibuprofen. However the following should be considered:
Ibuprofen has been reported to be associated with cognitive dysfunction in the elderly.
The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.
The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section 4.4).
Method of Administration:
For oral administration.
To be taken preferably with or after food.
The capsules should be swallowed whole with a liberal quantity of water.
4.3 Contraindications
- Hypersensitivity to Ibuprofen or to any of the excipients listed in section 6.1.
- NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs.
- Severe heart failure (NYHA Class IV), hepatic, failure and renal failure. (See section 4.4).
- During the last trimester of pregnancy (See section 4.6)
- Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
History of gastrointestinal bleeding or perforation, related to previous
NSAIDs therapy.
4.4. Special warnings and precautions for use
The use of Fenbid with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5)
If given to patients receiving anticoagulant therapy, prothrombin time should be monitored at least for the first few days of combined treatment.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).
Respiratory disorders:
Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
Renal disorders
Renal tubular acidosis and hypokalaemia may occur following acute overdose and in patients taking ibuprofen products over long periods at high doses (typically greater than 4 weeks), including doses exceeding the recommended daily dose.
Cardiovascular, Renal and Hepatic Impairment:
The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these patients (See also section 4.3 – Contraindications).
Cardiovascular and cerebrovascular effects:
Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.
Clinical studies suggest that use of ibuprofen, particularly at a high dose (2400mg/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. < 1200mg/daily) 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 be made before initiating longer-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.
Cases of Kounis syndrome have been reported in patients treated with Fenbid capsules. Kounis syndrome has been defined as cardiovascular symptoms secondary to an allergic or hypersensitive reaction associated with constriction of coronary arteries and potentially leading to myocardial infarction.
Gastrointestinal bleeding, ulceration and perforation:
GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAID at any time during treatment, with or without warning symptoms or a previous history of serious GI events.
The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4 3), and in the elderly. These patients should commence treatment on the lowest dose available Combination therapy with protective agents (e g misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4 5)
Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5 Interactions).
When GI bleeding or ulceration occurs in patients receiving Ibuprofen, the treatment should be withdrawn.
NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) as these conditions may be exacerbated (See section 4.8 – Undesirable effects).
SLE and mixed connective tissue disease:
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (See section 4.8 – Undesirable effects).
Severe cutaneous adverse reactions (SCARs): Severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, erythema multiforme, Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported in association with the use of ibuprofen (see section 4.8). Most of these reactions occurred within the first month. If signs and symptoms suggestive of these reactions appear ibuprofen should be withdrawn immediately and an alternative treatment considered (as appropriate).
There is a risk of renal impairment in dehydrated children and adolescents.
Impaired Female fertility:
The use of Ibuprofen may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal or Ibuprofen should be considered.
Elderly:
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (See section 4.2 – Posology and administration)
Masking of symptoms of underlying infections
Ibuprofen can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection. This has been observed in bacterial community acquired pneumonia and bacterial complications to varicella. When Ibuprofen is administered for fever or pain relief in relation to infection, monitoring of infection is advised. In nonhospital settings, the patient should consult a doctor if symptoms persist or worsen.
Important information regarding the excipients in this medicine:
Sucrose: Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Sodium: This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.
4.5. Interaction with other medicinal products and other forms of interaction
Fenbid Biphasic Capsules should be avoided in combination with:
Acetylsalicylic acid
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 (see section 5.1).
Other analgesics including cyclooxygenase—2 selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects (See section 4.4).
Anti-hypertensives: Reduced anti-hypertensive effect.
Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.
Lithium: Decreased elimination of lithium.
Methotrexate: Decreased elimination of methotrexate.
Ciclosporin: Increased risk of nephrotoxicity.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Corticosteroids: Increased risk of gastrointestinal bleeding (See section 4.4 – Special warnings and precautions for use).
Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (See section 4.4 – Special warnings and precautions for use).
Quinolone antibiotics: 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.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (See section 4.4).
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Zidovudine: Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of hemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
4.6 Fertility, Pregnancy and Lactation
Pregnancy:
Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern.
From the 20th week of pregnancy onward, Fenbid capsules use may cause oligohydramnios resulting from foetal renal dysfunction. This may occur shortly after treatment initiation and is usually reversible upon discontinuation. In addition, there have been reports of ductus arteriosus constriction following treatment in the second trimester, most of which resolved after treatment cessation. Therefore, during the first and second trimester of pregnancy, Fenbid capsules should not be given unless clearly necessary. If Fenbid capsules is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible. Antenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to Fenbid capsules for several days from gestational week 20 onward. Fenbid capsules should be discontinued if oligohydramnios or ductus arteriosus constriction are found.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:
- cardiopulmonary toxicity (with premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
- renal dysfunction (see above);
the mother and the neonate, at the end of pregnancy, to:
- possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses;
- inhibition of uterine contractions resulting in delayed or prolonged labour.
Consequently, Fenbid is contraindicated during the third trimester of pregnancy (see sections 4.3 and 5.3).
Breast-feeding:
In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.
Fertility:
See section 4.4 – Special warnings and precautions for use, regarding female fertility.
4.7 Effects on ability to drive and use machines
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
4.8. Undesirable effects
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 (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease (See section 4.4 – Special warnings and precautions for use) have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.
Hypersensitivity: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
Skin and subcutaneous tissue disorders:
Frequency very rare: Severe cutaneous adverse reactions (SCARs) (including Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis).
Frequency not known: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), Acute generalised exanthematous pustulosis (AGEP).
Cardiovascular and cerebrovascular:
Clinical studies suggest that use of ibuprofen, particularly at high dose (2400 mg/day) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).
Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.
Not known: Kounis syndrome.
Other adverse reactions reported less commonly include:
Renal and Urinary disorders: Nephrotoxicity in various forms, including interstitial nephritis, nephrotic Syndrome and renal failure. Not known: Renal tubular acidosis*
Hepatobiliary disorders: Abnormal liver function, hepatitis and jaundice.
Neurological and special senses: visual disturbances, optic neuritis, headaches, paraesthesia, reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation (See section 4.4), depression, confusion, hallucinations, tinnitus, vertigo, dizziness, malaise, fatigue and drowsiness.
Blood and lymphatic system disorders: Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia.
Metabolism and Nutrition Disorders: Hypokalaemia* (Not known).
Dermatological: Bullous reactions including Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (very rare). Photosensitivity reactions (frequency unknown).
Description of Selected Adverse Reactions
*Renal tubular acidosis and hypokalaemia have been reported in the post-marketing setting typically following prolonged use of the ibuprofen component at higher than recommended doses.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme website: www.mhra.gov.uk.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
In children ingestion of more than 400 mg/kg may cause symptoms. In adults the dose response effect is less clear cut. The half-life in overdose is 1.5-3 hours. In serious poisoning metabolic acidosis may occur.
- a) Symptoms
Symptoms include nausea, vomiting, epigastric pain, or more rarely diarrhoea. Tinnitus, headache and gastrointestinal bleeding are also possible. In more serious poisoning, toxicity is seen in the central nervous system, manifesting as drowsiness, dizziness, occasionally excitation and disorientation or coma. Occasionally patients develop convulsions. In serious poisoning metabolic acidosis may occur and the prothrombin time/ INR may be prolonged, probably due to interference with the actions of circulating clotting factors. Acute renal failure and liver damage may occur. Exacerbation of asthma is possible in asthmatics.
Prolonged use at higher than recommended doses or overdose may result in hypokalaemia and renal tubular acidosis. Symptoms may include reduced level of consciousness and generalised weakness (see section 4.4 and section 4.8).
- b) Therapeutic measures
Patients should be treated symptomatically as required.
Management should be supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable. Consider oral administration of activated charcoal if the patient presents within 1 hour of ingestion of a potentially toxic amount. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose. Good urine output should be ensured. Renal and liver function should be closely monitored. Patients should be observed for at least four hours after ingestion of potentially toxic amounts. If frequent or prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.
Other measures may be indicated by the patient’s clinical condition.
5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties
Ibuprofen is a recognised non-steroidal anti-inflammatory agent with marked analgesic and antipyretic properties.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Some pharmacodynamic studies show that when single doses of ibuprofen 400 mg were taken within 8 h before or within 30 min after immediate release acetylsalicylic acid dosing (81 mg), a decreased effect of acetylsalicylic acid on the formation of thromboxane or platelet aggregation occurred. 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 (see section 4.5).
5.2 Pharmacokinetic properties
The product is a combined immediate release and sustained release formulation of ibuprofen designed to ensure plasma levels in the therapeutic range for approximately 12 hours.
5.3 Preclinical safety data
No further information.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sugar spheres USP (containing maize starch and sucrose) Povidone BP
Sodium starch glycolate BP
6.2 Incompatibilities
None Known.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Store at room temperature below 25°C, protected from light and moisture.
6.5 Nature and contents of container
PVC (200-250μm)/PVDC (40gms) blisters and aluminium foil (20 μm).
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
BRISTOL LABORATORIES LIMITED
Unit 3, Canalside
Northbridge Road
Berkhamsted
Herts
HP4 1EG
UNITED KINGDOM
8 MARKETING AUTHORISATION NUMBER(S)
PL 17907/0293
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
05/12/2005
10 DATE OF REVISION OF THE TEXT
05/08/2024