Summary of medicine characteristics - IBUPROFEN PERRIGO 400 MG FILM-COATED TABLETS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen Perrigo 400mg Film-coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
400mg Ibuprofen (as Ibuprofen Lysine 684 mg)
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated Tablet [Tablet].
White, capsule – shaped, film-coated tablet, embossed on one side with ‘L684’.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
This medicine is indicated in adults and adolescents (12 years of age and above) for the symptomatic treatment of mild to moderate pain, such as headache, period pain, dental pain, and fever and pain in the common cold.
4.2 Posology and method of administration
For oral administration and short-term use only.
Adults and adolescents > 40 kg (12 years of age and above):
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
If this product is required for more than 3 days in the case of fever or for more than 4 days for the treatment of pain, or if the symptoms worsen the patient is advised to consult a doctor.
If in children and adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
Take 1 tablet with water, up to three times a day as required.
Leave at least 6 hours between doses.
Do not take more than 3 tablets in any 24 hour period.
It is recommended that patients with sensitive stomachs take Ibuprofen Perrigo 400mg Film-coated Tablets with food.
If in adolescents this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
Special patient groups
Paediatric population:
Not recommended for adolescents weighing under 40 kg or children under 12 years of age.
Elderly Population:
No special dose adjustment is required. Because of the possible undesirableeffect profile (see section 4.4), it is recommended to monitor the elderly particularly carefully.
Renal impairment:
No dose reduction is required in patients with mild to moderate impairment to renal function (patients with severe renal insufficiency, see section 4.3).
Hepatic impairment (see section 5.2):
No dose reduction is required in patients with mild to moderate impairment to hepatic function (patients with severe hepatic dysfunction, see section 4.3).
4.3 Contraindications
Hypersensitivity to the active substance or to any of the exipients listed in section 6.1.
Patients who have previously shown hypersensitivity reactions (e.g. bronchospasm, asthma, rhinitis, angioedema, or urticaria) associated with the intake of acetylsalicylic acid (aspirin) or other non-steroidal anti-inflammatory drugs (NSAIDs).
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.
Severe hepatic failure, severe renal failure or severe heart failure (see Section 4.4 Special warnings and precautions for use).
Patients with cerebrovascular or other active bleeding.
Patients with blood coagulation disorders.
Patients with unclarified blood-formation disturbances.
Patients with severe dehydration (caused by vomiting, diarrhea or insufficient fluid intake).
Last trimester of pregnancy (see Section 4.6 Pregnancy and lactation).
Severe heart failure (NYHA Class IV)
4.4 Special warnings and precautions for use
Caution is required in patients with certain conditions, which may be made worse:
Congenital disorder of porphyrin metabolism (e.g. acute intermittent porphyria).
Directly after major surgery.
In patients who react allergically to other substances, as an increased risk of hypersensitivity reactions occurring also exists for them on use of this medicine.
In patients who suffer from hayfever, nasal polyps or chronic obstructive respiratory disorders as an increased risk exists for them of allergic reactions occurring. These may present as asthma attacks (so-called analgesic asthma), Quincke’s oedema or urticaria.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see GI and cardiovascular risks below).
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
Prolonged use of any type of painkiller for headaches can make them worse. If this situation is experienced or suspected, medical advice should be obtained and treatment should be discontinued. The diagnosis of medication overuse headache (MOH) should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of headache medications.
Masking of symptoms of underlying infections
This product 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 this medicine is administered for fever or pain relief in relation to infection, monitoring of infection is advised. In non-hospital settings, the patient should consult a doctor if symptoms persist or worsen.
Respiratory:
Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma or allergic disease.
SLE and mixed connective tissue disease:
Systemic lupus erythematosus and mixed connective tissue disease – increased risk of aseptic meningitis (see section 4.8 Undesirable effects).
Other NSAIDs:
The use of this medicine with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).
Renal:
Hypertension and/or cardiac impairment as renal function may deteriorate and/or fluid retention occur.
Renal impairment as renal function may further deteriorate (See section 4.3
Contraindications and Section 4.8 Undesirable effects)
There is a risk of renal impairment in dehydrated adolescents.
Hepatic:
Hepatic dysfunction (See section 4.3 Contraindications and Section 4.8 Undesirable effects)
Gastrointestinal safety:
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)
Gastrointestinal bleeding, ulceration and perforation: GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of serious gastrointestinal 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 acetylsalicylic acid, or other drugs likely to increase gastrointestinal risk (See below and section
4.5).
Patients with a history of gastrointestinal toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially gastrointestinal 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 acetylsalicylic acid (see section 4.5).
When gastrointestinal bleeding or ulceration occurs in patients receiving this medicine, the treatment should be withdrawn.
Severe skin reactions:
Serious skin reactions, some of them fatal, including exfoliative dermatitis,
Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDSs (see section 4.8). Patients appear to be at highest risk for these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Acute generalised exanthematous pustulosis (AGEP) has been reported in relation to ibuprofen-containing products. This medicine should be discontinued at the first appearance of signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions, or any other sign of hypersensitivity.
Exceptionally, varicella can be at the origin of serious cutaneous and soft tissues infectious complications. To date, the contributing role of NSAIDs in the worsening of these infections cannot be ruled out. Thus, it is advisable to avoid use of this medicine in case of varicella.
Cardiovascular and cerebrovascular effects:
Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.
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.
Other notes:
Severe acute hypersensitivity reactions (for example anaphylactic shock) are observed very rarely. At the first signs of hypersensitivity reaction after taking/administering this medicine therapy must be stopped. Medically required measures, in line with the symptoms, must be initiated by specialist personnel.
In prolonged administration of this medicine regular checking of the liver values, the kidney function, as well as of the blood count, is required.
In general terms, the habitual intake of painkillers, particularly on combination of several pain- relieving active substances, may lead to permanent renal damage with the risk of renal failure (analgesic nephropathy). This risk may be increased under physical strain associated with loss of salt and dehydration. Therefore it should be avoided.
Through concomitant consumption of alcohol, active substance-related undesirable effects, particularly those that concern the gastrointestinal tract or the central nervous system, may be increased on use of NSAIDs.
4.5 Interaction with other medicinal products and other forms of interaction
Ibuprofen should not be used in combination with:
Acetylsalicylic acid (Aspirin):
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 NSAIDS including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs as this may increase the risk of gastrointestinal ulcers and bleeding due to a synergistic effect (see section 4.4).
Ibuprofen should be used with caution in combination with:
Anticoagulants: NSAIDS may enhance the effects of anti-coagulants, such as warfarin (See section 4.4).
Phenytoin:
The concomitant use of ibuprofen with phenytoin may increase serum levels of both substances. A check of serum-phenytoin levels is not as a rule required on correct use (maximum over 4 days).
Antihypertensives and diuretics:
NSAIDs may diminish the effect of these drugs. Diuretics can increase the risk of nephrotoxicity of NSAIDs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor, betareceptor-blockers or angiotensin-II antagonists and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.
Potassium sparing diuretics:
The concomitant administration of ibuprofen and potassium-sparing diuretics may lead to hyperkalaemia (check of serum potassium is recommended).
Corticosteroids:
Increased risk of gastrointestinal ulceration or bleeding (See section 4.4 Special warnings).
Antiplatlet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (see section 4.4)
Digoxin:
The concomitant use of Ibuprofen Perrigo with digoxin preparations may increase serum levels of these medicinal products. A check of serum-digoxin is not as a rule required on correct use (maximum over 4 days).
Lithium:
The concomitant use of Ibuprofen Perrigo with lithium preparations may increase serum levels of these medicinal products. A check of serum-lithium is not as a rule required on correct use (maximum over 4 days).
Probenecid and sulfinpyrazone:
Medicinal products that contain probenecid or sulfinpyrazone may delay the excretion of ibuprofen.
Methotrexate:
The administration of ibuprofen within 24 hours before or after administration of methotrexate may lead to elevated concentrations of methotrexate and an increase in its toxic effect.
Ciclosporin: Increased risk of nephrotoxicity.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Zidovudine:
There is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
Sulphonylureas:
Clinical investigations have shown interactions between nonsteroidal antiinflammatory drugs and antidiabetics (sulphonylureas). Although interactions between ibuprofen and sulphonylureas have not been described to date, a check of blood-glucose values is recommended as a precaution on concomitant intake.
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.
4.6 Fertility, pregnancy and lactation
Fertility
There is limited evidence that drugs which inhibit cyclo-oxygenase/ prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible upon withdrawal of treatment.
Pregnancy
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5 %. The risk is believed to increase with dose and duration of therapy.
In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period.
During the first and second trimester of pregnancy, ibuprofen should not be given unless clearly necessary. If ibuprofen 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.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose
the foetus to:
o cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
o renal dysfunction, which may progress to renal failure with oligohydroamniosis;
the mother and the neonate, at the end of pregnancy, to:
o possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.
o inhibition of uterine contractions resulting in delayed or prolonged labour.
Consequently, ibuprofen is contraindicated during the third trimester of pregnancy.
Lactation
Ibuprofen and its metabolites can pass in low concentrations into the breast milk. No harmful effects to infants are known to date, so for the short-term treatment with the recommended dose for pain and fever interruption of breast-feeding would generally not be necessary.
4.7 Effects on ability to drive and use machines
As central nervous undesirable effects such as tiredness and dizziness may occur on use of Ibuprofen Perrigo 400mg Film-coated Tablets at high dosage, the ability to react and the ability to take part actively in road traffic and to operate machines may be impaired in isolated cases. This applies to a greater extent in combination with alcohol.
4.8 Undesirable effects
For the frequency of occurrence of side effects, the following phrases are used: Very common (> 1/10)
Common (> 1/100 to <1/10) Uncommon (> 1/1,000 to <1/100) Rare (> 1/10,000 to <1/1,000)
Very rare (<1/10,000), not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
The most commonly observed adverse reactions 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) have been reported following administration. Less frequently, gastritis has been observed.
Oedema, hypertension and cardiac 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 (for example myocardial infarction or stroke) (see section 4.4).
The list of the following undesirable effects comprises all undesirable effects that have become known under treatment with ibuprofen, also those under high-dose long-term therapy in
rheumatism patients. The stated frequencies, which extend beyond very rare reports, refer to the short-term use of daily doses up to a maximum of 1200 mg ibuprofen for oral dosage forms and a maximum of 1800 mg for suppositories.
With the following adverse drug reactions, it must be accounted for that they are predominantly dose-dependent and vary interindividually.
Infections and infestations:
Very rare: Exacerbation of infection-related inflammations (e.g. development of necrotising fasciitis) coinciding with the use of nonsteroidal antiinflammatory drugs has been described. This is possibly associated with the mechanism of action of the nonsteroidal antiinflammatory drugs.
If signs of an infection occur or get worse during use of this medicine, the patient is therefore recommended to go to a doctor without delay. It is to be investigated whether there is an indication for an antiinfective/antibiotic therapy.
The symptoms of aseptic meningitis with neck stiffness, headache, nausea, vomiting, fever or consciousness clouding have been observed under ibuprofen. Patients with autoimmune disorders (SLE, mixed connective-tissue disease) appear to be predisposed.
Blood and Lymphatic System Disorders:
Very rare: Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, agranulocytosis). First signs are: fever, sore throat, superficial mouth ulcers, flu-like symptoms,
severe exhaustion, unexplained bleeding and bruising. In such cases the patient should be
advised to discontinue the medicine immediately, to avoid any self-medication with analgesics or antipyretics and to consult a physician. The blood count should be checked regularly in long- term therapy.
Immune System Disorders:
Uncommon: Hypersensitivity reactions with skin rashes and pruritus, as well as asthma attacks (possibly with drop in blood pressure), aggravated asthma, bronchospasm, dyspnoea. The patient is to be instructed to inform a doctor at once and no longer to take this medicine in this case.
Very rare: Severe general hypersensitivity reactions. Symptoms could be: facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock). If one of these symptoms occurs, which can happen even on first use, the immediate assistance of a doctor is required.
Psychiatric disorders:
Very rare: Psychotic reactions, depression.
Nervous System Disorders:
Uncommon: Central nervous disturbances such as headache, dizziness, sleeplessness, agitation, irritability or tiredness.
Eye disorders:
Uncommon: Visual disturbances.
Ear and labyrinth disorders:
Rare: Tinnitus.
Cardiac Disorders:
Very rare: Palpitations, cardiac failure, myocardial infarction.
Vascular Disorders:
Very rare: Arterial hypertension.
Respiratory, Thoracic and Mediastinal Disorders:
Very rare: Exacerbation of asthma, brochospasm, dyspnoea.
Gastrointestinal Disorders:
Common: Gastro-intestinal complaints such as pyrosis, abdominal pain, nausea, vomiting, flatulence, diarrhoea, constipation and slight gastro-intestinal blood losses that may cause anaemia in exceptional cases.
Uncommon: Gastrointestinal ulcers, potentially with bleeding and perforation. Ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4), gastritis.
Very rare: Oesophagitis, pancreatitis, formation of intestinal diaphragm-like strictures. The patient is to be instructed to withdraw the medicinal product and to go to a doctor immediately if severe pain in the upper abdomen or melaena or haematemesis occurs.
Hepatobiliary Disorders:
Very rare: Hepatic dysfunction, hepatic damage, particularly in long-term therapy, hepatic failure, acute hepatitis.
Skin and Subcutaneous Tissue Disorders:
Uncommon: Various skin rashes
Very rare: Severe forms of skin reactions such as bullous reactions, including Stevens-Johnson
Syndrome, erythema multiforme and toxic epidermal necrolysis can occur.
Alopecia. In exceptional cases, severe skin infections and soft-tissue complications may occur during a varicella infection (see also „Infections and infestations“).
Not known: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalised exanthematous pustulosis (AGEP), photosensitivity reactions.
Renal and Urinary Disorders:
Rare: Kidney-tissue damage (papillary necrosis) and elevated uric acid concentrations in the blood may also occur rarely.
Very rare: Formation of oedemas, particularly in patients with arterial hypertension or renal insufficiency, nephrotic syndrome, interstitial nephritis that may be accompanied by acute renal insufficiency. Renal function should therefore be checked regularly.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store
4.9 Overdose
4.9 OverdoseIn adolescents and adults the dose response effect is not clear cut in overdose.
The half-life in overdose is 1.5–3 hours.
Symptoms
Most patients who have ingested clinically important amounts of NSAIDs will develop no more than 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 dizziness, drowsiness, 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.
Management
Management should be symptomatic and supportive and include the maintainance 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. If frequent or prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, non-steroids; propionic acid derivative.
ATC code: M01AE01
Ibuprofen lysine is the lysine salt of ibuprofen. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that in the conventional animal-experiment inflammation models has proven to be effective via prostaglandin-synthesis inhibition. In humans ibuprofen reduces inflammatory-related pain, swellings and fever.
Furthermore, Ibuprofen reversibly inhibits ADP- and collagen-induced platelet aggregation.
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
Most pharmacokinetic data obtained following the administration of ibuprofen acid also apply to ibuprofen lysine.
On oral application, ibuprofen is partly absorbed in the stomach and then completely in the small intestine.
Following hepatic metabolisation (hydroxylation, carboxylation), the pharmacologically inactive metabolites are completely eliminated, mainly renally (90 %), but also with the bile. The elimination half-life in healthy individuals and those with liver and kidney diseases is 1.8 – 3.5 hours, plasmaprotein binding about 99 %.
Peak plasma levels following oral administration of a normal-release pharmaceutical form (tablet) when taken with food are reached after 1 – 2 hours.
Peak plasma levels following oral administration of a normal-release pharmaceutical form (tablet) when taken under fasting conditions are reached after 60 to 90 minutes. However ibuprofen is absorbed more rapidly from the gastrointestinal tract following oral administration of Ibuprofen Perrigo 400mg Film-coated Tablets with peak plasma levels following oral administration under fasting conditions reached after 30 minutes (median). Ibuprofen is detected in the plasma for more than 8 hours after administration of Ibuprofen Perrigo 400mg Film-coated Tablets.
5.3 Preclinical safety data
5.3 Preclinical safety dataThe subchronic and chronic toxicity of ibuprofen in animal experiments showed up mainly in form of lesions and ulcerations in the gastro-intestinal tract. In vitro and in vivo studies gave no clinically relevant evidence of a mutagenic potential of ibuprofen. In studies in rats and mice no evidence of carcinogenic effects of ibuprofen was found. Ibuprofen led to an inhibition of ovulation in rabbits as well as disturbances of implantation in various animal species (rabbit, rat, mouse). Experimental studies in rats and rabbits have demonstrated that ibuprofen crosses the placenta. For maternally toxic doses, an increased incidence of malformations (ventricular septal defects) was observed in the progeny of rats.
The active substance ibuprofen shows an environmental risk to fish.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Core
Crospovidone
Copovidone
Microcrystalline Cellulose
Magnesium Stearate
Coat
Opadry II White
Contains the constituents; polyvinyl alcohol, titanium dioxide, macrogol and talc.
6.2 Incompatibilities
Not applicable
6.3 Shelf life
36 months
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.