Produktinformationen för Ibuprofen Farmalider 20 mg/ml, 40 mg/ml oral suspension, MTnr
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SUMMARY OF PRODUCT CHARACTERISTICS
1
NAME OF THE MEDICINAL PRODUCT
Ibuprofen Farmalider 20 mg/ml oral suspension
Ibuprofen Farmalider 40 mg/ml oral suspension
2
QUALITATIVE AND QUANTITATIVE COMPOSITION
One ml of oral suspension contains 20 mg ibuprofen.
One ml of oral suspension contains 40 mg ibuprofen.
Excipients with known effect: Saccharin sodium 0,5 mg/ml and maltitol liquid 500 mg/ml.
For the full list of excipients, see section 6.1.
3
PHARMACEUTICAL FORM
Oral suspension.
White or off-white suspension with strawberry flavour.
4
CLINICAL PARTICULARS
4.1
Therapeutic indications
Symptomatic treatment of
- fever
‐ mild to moderate pain such as dental pain, post-surgical pain, headache (including migraine),
and musculoskeletal pain (e.g. backache, minor injuries such as sprains and strains)
‐ painful conditions (e.g. sore throat and earache) caused by pharyngitis, tonsillitis and otitis
‐ dysmenorrhoea
Children 6 months - 12 years (> 7 kg):
Acute painful conditions and fever associated with upper respiratory tract infection
4.2
Posology and method of administration
Treatment should be initiated with the lowest possible effective dose, so that later on it can be adjusted
on the basis of the therapeutic response and possible adverse effects. In the long-term treatment one
must aim at low maintenance dose.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration
necessary to control symptoms (see section 4.4).
20 mg/ml:
Adults and children over 12 years:
Fever, mild to moderate pain and painful conditions:
200 mg-400 mg (10-20 ml) as a single dose or 3- 4 times daily, however maximal daily dose is 1200
mg (60 ml). The interval between two doses should be at least 4 hours. Single doses over 400 mg (20
ml) have not shown to give any additive analgesic effect.
Dysmenorrhoea: 400 mg (20 ml) 1-3 times daily, as required. An interval of at least 4-6 hours should
be allowed between doses. Treatment should start at the first sign of menstruation discomfort
Children 6months - 12 years (> 7 kg):
Acute painful conditions and fever associated with upper respiratory tract infection:
5-7.5 mg ibuprofen/kg body weight as a single dose or 20-30 mg/kg body weight per day according to
the table below. Body weight should be used when calculating the dose (the ages given are
approximate).
Weight
7-10 kg
10-14.5 kg
14.5-25 kg
25-40 kg
Age
6-12 months
1-2 years
3-7 years
8-12 years
Dose
2.5 ml 3 times daily
2.5 ml 3-4 times daily
5 ml 3-4 times daily
10 ml 3-4 times daily
The dose should be given every 6 hours, up to four times daily. Not to be given to children under the
age of six months or children who weigh less than 7 kg.
40 mg/ml:
Adults and children over 12 years:
Fever, mild to moderate pain and painful conditions:
200 mg-400 mg (5-10 ml) as a single dose or 3- 4 times daily, however maximal daily dose is 1200
mg (30 ml). The interval between two doses should be at least 4 hours. Single doses over 400 mg (10
ml) have not shown to give any additive analgesic effect.
Dysmenorrhoea: 400 mg (10 ml) 1-3 times daily, as required. An interval of at least 4-6 hours should
be allowed between doses. Treatment should start at the first sign of menstruation discomfort.
Children 6 months - 12 years (> 7 kg):
Acute painful conditions and fever associated with upper respiratory tract infection:
5-7.5 mg ibuprofen/kg body weight as a single dose or 20-30 mg/kg body weight per day according to
the table below. Body weight should be used when calculating the dose (the ages given are
approximate).
Weight
7-10 kg
10-14.5 kg
14.5-25 kg
25-40 kg
Age
6-12 months
1-2 years
3-7 years
8-12 years
Dose
1 ml 3 times daily
1 ml 3-4 times daily
2.5 ml 3-4 times daily
5 ml 3-4 times daily
The dose should be given every 6 hours, up to four times daily. Not to be given to children under the
age of six months or children who weigh less than 7 kg. For children under 8 years, Ibuprofen
Farmalider 20 mg/ml oral suspension is recommended in order to give more accurate dosing.
Elderly
The elderly are at increased risk of 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. If renal or hepatic
function is impaired, dosage should be assessed individually.
Renal impairment
Caution should be taken with ibuprofen dosage in patients with renal impairment. The dosage should
be assessed individually. The dose should be kept as low as possible and renal function should be
monitored (see sections 4.3, 4.4 and 5.2).
Hepatic impairment
Caution should be taken with dosage in patients with hepatic impairment. The dosage should be
assessed individually and the dose should be kept as low as possible (see sections 4.3, 4.4 and 5.2).
4.3
Contraindications
Hypersensitivity to ibuprofen or to any of the excipients listed in section 6.1.
Because of cross reaction Ibuprofen Farmalider should not be given to patients who have experienced
symptoms of asthma, rhinitis or urticaria associated with intake of acetylsalicylic acid or other
nonsteroidal anti-inflammatory drugs.
Conditions with increased tendency to bleeding.
Cerebrovascular or other active bleeding.
History of gastrointestinal (GI) bleeding or perforation, related to previous NSAIDs therapy.
Active gastric or duodenal ulcer or history of recurrent peptic ulcer/haemorrhage (two or more
distinct episodes of proven ulceration or bleeding).
Severe hepatic failure.
Severe heart failure
Severe renal disease (glomerular filtration below 30 ml/minute) (see section 4.4).
Third trimester of pregnancy (see section 4.6).
4.4
Special warnings and precautions for use
The use of Ibuprofen Farmalider with concomitant NSAIDs including cyclooxygenase-2 selective
inhibitors should be avoided.
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). Therefore the
lowest effective dose should be individually adjusted for every patient.
As with other NSAIDs, ibuprofen may mask the signs of infection.
Elderly:
The elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal
(GI) bleeding and/or perforation, which may be fatal. The elderly patients more often have impaired
renal, cardiac or liver function.
Gastrointestinal bleeding, ulceration and perforation:
Patients with a history of GI adverse reactions, particularly when elderly, should report any unusual
abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
Caution should be advised in treatment of elderly patients, who generally have an increased frequency
of adverse reactions. Consequences, e.g. gastrointestinal haemorrhage and/or perforation, become
often more severe in the elderly and they may appear without warning symptoms and even though
they have not manifested in the past.
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).
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 possible dose.
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).
Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has been reported with all
NSAIDs at any time during treatment, with or without warning symptoms or a previous history of
serious GI events.
When GI bleeding or ulceration occurs in patients receiving Ibuprofen Farmalider, 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 their condition may be exacerbated (see section 4.8).
Renal effects
Ibuprofen should be used with caution and lower doses in patients with impaired renal or hepatic
function, and in the elderly patients. Renal function should be monitored periodically during long-term
ibuprofen therapy. Ibuprofen is contraindicated in patients with severe renal impairment (see section
4.3).
Caution should be exercised with regard to dehydrated patients.
As with other NSAIDs, the long-term administration of ibuprofen has resulted in papillary necrosis
and other pathological changes in the kidney. Renal toxicity has also been seen in patients in whom
renal prostaglandins have a compensatory role in the maintenance of normal renal perfusion. In these
patients the administration of an NSAID may cause a dose-dependent reduction in prostaglandin
formation and, secondarily, in renal blood flow, which may cause kidney failure. Those who are at
greatest risk of this are patients with renal impairment, heart failure, liver dysfunction, the elderly and
patients on diuretics or ACE inhibitors. The symptoms are normally reversible following withdrawal
of the NSAID.
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 trial and epidemiological data suggest that use of ibuprofen, particularly at a high dose (2400
mg daily) and in long term treatment may be associated with a small increased risk of arterial
thrombotic events (e.g. 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
myocardial infarction.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease,
peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after
careful consideration. Similar consideration should be made before initiating longer-term treatment of
patients with risk factors for cardiovascular disease (e.g., hypertension, hyperlipidaemia, diabetes
mellitus, smoking).
Skin reactions
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnsons
syndrome, and toxic epidermal necrolysis, have been reported (very rarely) in association with the use
of NSAIDs (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. Ibuprofen Farmalider should be discontinued at the first appearance of 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 Ibuprofen Farmalider in case of varicella.
Patients with gastrointestinal problems, SLE, haematological or coagulation disorders and asthma
should be treated with care and be closely monitored during NSAID treatment, since their condition
may be exacerbated by the NSAID. Ibuprofen can inhibit platelet aggregation, resulting in
prolongation of bleeding time.
Respiratory disorders
Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial
asthma or allergic disease.
Aseptic meningitis
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.
Fertility
Use of Ibuprofen Farmalider may decrease fertility and therefore it is not recommended for women
who attempting to get pregnant. This considers all drugs that inhibit cyclo-oxygenase/prostaglandin
synthesis. The effect is reversible and it ceases when the exposure to this type of drugs is ended.
Ibuprofen Farmalider oral suspension contains maltitol. Patients with rare hereditary problems of
fructose intolerance should not take this medicine.
4.5
Interaction with other medicinal products and other forms of interaction
Following combinations with Ibuprofen Farmalider should be avoided:
Acetylsalicylic acid. NSAID-products should not be combined with acetylsalicylic acid because of
increased risk of bleeding.
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet
aggregation when they are dosed concomitantly. However, the limitations of these data and the
uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm
conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be
likely for occasional ibuprofen use (see section 5.1).
Other NSAIDs. Concomitant use of NSAIDs with ibuprofen should be avoided due to increased risk of
gastrointestinal adverse reactions. Combined use of two or more different NSAIDs does not contribute
to the efficacy of the therapy and is potentially harmful.
Methotrexate. NSAIDs inhibit the tubular secretion of methotrexate and some metabolic interaction
with reduced clearance of methotrexate may also occur as a result. Accordingly, in high-dose
treatment with methotrexate one should always avoid prescribing NSAIDs (see below).
Anti-platelet agents: NSAIDs should not be combined with antiplatelet agents such as ticlopidine due
to an additive inhibition of platelet function
The dicumarol group. NSAIDs may enhance the effects of anticoagulants, such as warfarin (see
section 4.4). Experimental studies show that ibuprofen potentiates warfarin’s effects on bleeding time.
NSAIDs and the dicumarol group are metabolised by the same enzyme, CYP 2C9.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce the glomerular filtration and
increase the levels of cardiac glycosides (eg. digoxin) in plasma.
Mifepristone: A decrease in efficacy may theoretically occur due to anti-prostaglandin properties of
non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin. Limited experience suggests that
administration of NSAIDs on the day of prostaglandin administration does not adversely affect
efficacy of mifepristone and prostaglandin for cervical ripening or uterine contractility, nor affected
the clinical efficacy of medical abortion.
Sulphonylureas: There are rare reports of hypoglycaemia in patients on sulphonylurea medications
receiving ibuprofen.
Zidovudine: There is evidence of an increased risk of haemarthroses and haematoma in HIV(+)
haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
Following combinations with Ibuprofen Farmalider may need dose adjustment:
NSAIDs may reduce the effect of diuretics and other antihypertensive medicinal products.
ACE inhibitors and angiotensin II- antagonists. The risk of acute renal insufficiency, which is usually
reversible, may be increased in patients with impaired renal function (e.g. dehydrated patients and/or
elderly patients) when ACE-inhibitors or angiotensin II-receptor antagonists are combined with
NSAIDs, including selective cyclooxogenase-2-inhibitors. Therefore, the combination should be
administered with caution to patients with impaired renal function, 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 (see section 4.4).
Beta-blockers. NSAID type anti-inflammatory drugs reduce the antihypertensive effect of betaadrenoceptor blocking drugs.
Anti-platelet agents. Concomitant treatment increase the risk for gastrointestinal bleeding (see section
4.4).
Selective serotonin reuptake inhibitors, SSRIs. SSRI and NSAID each involve an increased risk of
bleeding e.g. from the gastrointestinal channel. This risk increases at concomitant treatment. The
mechanism may be associated with a decreased uptake of serotonin in the thrombocytes (see section
4.4).
Corticosteroids. Increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Ciclosporin and tacrolimus. It is presumed that administering of NSAID-drugs concomitantly with
ciclosporin or tacrolimus may increase the risk of nephrotoxicity because of decreased prostacyclin
synthesis in kidney. Therefore in combination treatment renal function must be carefully monitored.
Lithium. 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.
Colestyramine. The concomitant administration of ibuprofen and colestyramine retards and reduces
(by 25%) the absorption of ibuprofen. These drugs should be taken at least 2 hours apart.
Diuretics. NSAID-drugs (indomethacin and propionic acid derivatives) can reduce the diuretic effect
of furosemide and bumetanide (loop diuretics), possibly by inhibiting prostaglandin synthesis. They
can also decrease the antihypertensive effect of thiazides. Diuretics can increase the nephrotoxicity of
NSAIDs.
The concomitant administration of ibuprofen and potassium-sparing diuretics may lead to
hyperkalemia.
CYP2C9 Inhibitors. 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.
Aminoglycosides. NSAIDs may reduce the excretion of aminoglycosides. Children: Caution should be
exercised when co-administering ibuprofen and aminoglycosides.
Captopril: Experimental studies suggest that ibuprofen counteracts the effect of captopril on sodium
excretion.
Methotrexate: 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 and NSAID and methotrexate are given within 24 hours of one
another, as the plasma levels of methotrexate may increase, resulting in increased toxicity (see above).
Thrombolytics: Increased risk of gastrointestinal bleeding (see above).
Interaction studies have only been performed on adults.
4.6
Fertility, pregnancy and lactation
Pregnancy
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or embryo/foetal
development. Data from epidemiological studies suggest an increased risk of miscarriage and of
cardiac malformation and gastroschisis after the use of a prostaglandin synthesis inhibitor in early
pregnancy. The absolute risk of 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 the
administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and
post-implantation losses 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 trimesters of
pregnancy, Ibuprofen Farmalider should not be given unless clearly necessary. If Ibuprofen Farmalider
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, all prostaglandin synthesis inhibitors may expose the foetus to:
- Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary
hypertension),
- Renal dysfunction, which may progress to renal failure with consequent oligohydramnios.
The mother and the neonate, at the end of pregnancy, to:
- Prolongation of bleeding time,
- Inhibition of uterine contractions, which may result in delayed or prolonged labour.
Consequently, Ibuprofen Farmalider is contraindicated during the last trimester of pregnancy.
Breast-feeding
Ibuprofen is excreted in breast milk, but with therapeutic doses during short term treatment the risk for
influence on infant seems unlikely. If, however, longer treatment is prescribed, early weaning should
be considered.
Fertility
The use of ibuprofen may impair fertility and is not recommended in women attempting to conceive.
In women who have difficulties conceiving or who are undergoing investigation of infertility,
withdrawal of ibuprofen should be considered.
4.7
Effects on ability to drive and use machines
Treatment with ibuprofen may cause visual disturbances as an adverse effect. These effects are
uncommon but must be kept in mind when sharp attention is needed e.g. when driving a car.
4.8
Undesirable effects
The undesirable effects are mainly related to the pharmacological effect of ibuprofen on prostaglandin
synthesis. The most commonly observed adverse effects are gastrointestinal in nature. In occasional
use, with a maximum daily dose of 1200 mg, the adverse effects are less common.
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).
System organ class
Frequencies
Common (>1/100)
Uncommon (1/100-1/1000)
Blood and lymphatic
system disorders
Immune system
disorders
Psychiatric disorders
Nervous system
disorders
Eye disorders
Ear and labyrinth
disorders
Cardiac disorders
Vascular disorders
Respiratory, thoracic and
mediastial disorders
Gastrointestinal
disorders
Aplastic anaemia,
leucopenia,
thrombocytopenia
Anaphylactic reactions
Insomnia, mild anxiety
Headache
Visual disturbances
Hearing effects
Depression, confusion
Aseptic meningitis,
dizziness, somnolence,
optic neuritis
Toxic amblyopia
Tinnitus
Heart failure
Hypertension
Vomiting, diarrhoea,
abdominal pain,
dyspepsia, nausea,
constipation
Asthma, bronchospasm,
dyspnea, rhinitis
Hemorrhages, ulcus,
ulcerative stomatitis
Hepatobiliary disorders
Skin and subcutaneous
tissue disorders
Rare (< 1/1000)
Eczema
Angioedema, urticaria,
purpura, itching
Perforation, pancreatitis,
haematemesis, melena,
colitis, exacerbation of
ulcerative colitis and
Crohn´s disease,
gastritis, flatulence
Hepatic injuries,
hepatitis, jaundice and
elevation of liver
enzymes
Bullous reactions
including StevensJohnson syndrome, toxic
Renal and urinary
disorders
General disorders and
administration site
conditions
Tiredness
epidermal necrolysis,
erythema multiforme,
photosensitivity,
alopecia
Acute renal failure and
interstitial nephritis,
renal papillary necrosis,
nephrotic syndrome,
renal impairment
Oedema, fluid retention
Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, particularly in the elderly, may
occur (see section 4.4).
Exceptionally, occurrence of serious cutaneous and soft tissues infectious complications during
varicella have been reported.
Ibuprofen may cause prolongation in bleeding time by reversible inhibition of thrombocyte
aggregation. In most cases when aseptic meningitis has been reported some form of underlying
autoimmune disease (such as systematic lupus erythmatosus, and related connective tissue disease) has
existed. It has also been reported in patients who do not have underlying chronic disease.
Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.
Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at a high dose (2400
mg daily) and in long term treatment may be associated with a small increased risk of arterial
thrombotic events (e.g. myocardial infarction or stroke, see section 4.4).
4.9
Overdose
Toxicity: There is a risk of symptoms with doses >80-100 mg/kg. At doses >200 mg/kg there is a risk
of severe symptoms, though with considerable variations between individuals. A dose of 560 mg/kg
caused severe intoxication for 15 months old child. 3,2 g to 6-year-old child caused mild to moderate
intoxication, 2.8 –4 g to 1½-year-old child and 6 g to 6-year-old child after gastric lavage caused
severe intoxication, 8 g to an adult caused moderate and > 20 g to an adult very severe intoxication. 8
g to a 16-year-old affected the kidney and 12 g in combination with alcohol administered to a teenager
resulted in acute tubular necrosis.
Symptoms: Nausea, abdominal pain, vomiting (eventually bloody). Headache, tinnitus, dazed,
unconsciousness, cramps. Nystagmus, blurred vision. At high doses loss of consciousness,
convulsions (mainly in children). Bradycardia, hypotension. Metabolic acidosis, hypernatremia, renal
effects, hematuria, possibly liver impairment. Hypothermia. Isolated cases of ARDS.
Treatment: No special antidote is available. If needed gastric lavage, activated charcoal. Antacids if
needed. In the event of hypotension, intravenous fluid and, if required, inotropic support. Ensure
adequate diuresis. Correction of acid-base balance and electrolyte disturbances. General symptomatic
treatment.
5
PHARMACOLOGICAL PROPERTIES
5.1
Pharmacodynamic properties
Pharmacotherapeutic classification: Anti-inflammatory and antirheumatic products, non-steroids;
propionic acid derivatives, ATC code: M01AE01
Ibuprofen Farmalider belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs). It
contains the propionic acid derivative p-isobutyl-hydrotropic acid with the generic name ibuprofen.
Ibuprofen has anti-inflammatory, analgesic and antipyretic effects. The anti-inflammatory effect is
comparable with that of aspirin and indometacin. The pharmacological properties of are thought to
result from its ability to reduce prostaglandin synthesis. Ibuprofen prolongs bleeding time by
reversible inhibition of thrombocyte aggregation.
Ibuprofen inhibits the renal prostacyclin synthesis. This effect has not great importance in patients
with normal renal function. In patients with chronic renal insufficiency, cardiac insufficiency or
hepatic insufficiency and also in situations with changes in plasma volume the reduced prostaglandin
synthesis may lead to acute renal insufficiency, fluid retention and heart failure (see section 4.3 and
4.4).
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet
aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400 mg
was taken within 8 h before or within 30 min after immediate release aspirin dosing (81 mg), a
decreased effect of ASA on the formation of thromboxane or platelet aggregation occurred. However,
the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical
situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically
relevant effect is considered to be likely for occasional ibuprofen use.
5.2
Pharmacokinetic properties
Absorption
Ibuprofen is rapidly absorbed from the gastrointestinal tract with a bioavailability of 80-90%. Peak
serum concentrations occur one to two hours after administration. Studies including a standard meal
show that food does not markedly affect total bioavailability.
Distribution
Ibuprofen is extensively bound to plasma proteins (99%). Ibuprofen has a small volume of distribution
being about 0.12-0.2 l/kg in adults.
Biotransformation
Ibuprofen is rapidly metabolized in the liver through cytochrome P450, preferentially CYP2C9, to two
primary inactive metabolites, 2-hydroxyibuprofen and 3-carboxyibuprofen. Following oral ingestion
of the drug, slightly less than 90% of an oral dose of ibuprofen can be accounted for in the urine as
oxidative metabolites and their glucuronic conjugates. Very little ibuprofen is excreted unchanged in
the urine.
Elimination
Excretion by the kidney is both rapid and complete. The elimination half-life is approximately 2 hours.
The excretion of ibuprofen is virtually complete 24 hours after the last dose.
Special populations
Elderly
Given that no renal impairment exists, there are only small, clinically insignificant differences in the
pharmacokinetic profile and urinary excretion between young and elderly.
Children
The systemic exposure of ibuprofen following weight adjusted therapeutic dosage (5 mg/kg to 10
mg/kg bodyweight) in children aged 1 year or over, appears similar to that in adults. Children 3
months to 2.5 years appeared to have a higher volume of distribution (L/kg) and clearance (L/kg/h) of
ibuprofen than did children >2.5 to 12 years of age.
Renal impairment
For patients with mild renal impairment increased unbound (S)-ibuprofen, higher AUC values for (S)ibuprofen and increased enantiomeric AUC (S/R) ratios as compared with healthy controls have been
reported.
In end-stage renal disease patients receiving dialysis the mean free fraction of ibuprofen was about 3%
compared with about 1% in healthy volunteers. Severe impairment of renal function may result in
accumulation of ibuprofen metabolites. The significance of this effect is unknown. The metabolites
can be removed by haemodialysis (see sections 4.2, 4.3 and 4.4).
Hepatic impairment
Alcoholic liver disease with mild to moderate hepatic impairment did not result in substantially altered
pharmacokinetic parameters.
In cirrhotic patients with moderate hepatic impairment (Child Pugh’s score 6-10) treated with racemic
ibuprofen an average 2-fold prolongation of the half-life was observed and the enantiomeric AUC
ratio (S/R) was significantly lower compared to healthy controls suggesting an impairment of
metabolic inversion of (R)-ibuprofen to the active (S)-enantiomer (see sections 4.2, 4.3 and 4.4).
5.3
Preclinical safety data
There are no preclinical data considered relevant to clinical safety beyond data included in other
sections of this Summary of product characteristics.
6
PHARMACEUTICAL PARTICULARS
6.1
List of excipients
Saccharin sodium
Sodium benzoate (E211)
Citric acid, anhydrous
Sodium citrate
Hypromellose
Xanthan gum
Maltitol (E965)
Glycerol
Thaumatin (40 mg/ml oral suspension only)
Strawberry flavour
Purified water
6.2
Incompatibilities
Not applicable.
6.3
Shelf life
3 years.
20 mg/ml: After first opening, the shelf-life is 6 months when stored below 25°C.
40 mg/ml: After first opening, the shelf-life is 6 months when stored below 30°C.
6.4
Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5
Nature and contents of container
PET bottle with HDPE child-proof cap and LDPE stopper.
A 5 ml syringe is provided.
20 mg/ml: Pack sizes: 100 ml, 150 ml or 200 ml.
40 mg/ml: Pack sizes: 30 ml, 100 ml, 150 ml or 200 ml.
Not all pack sizes may be marketed.
6.6
Special precautions for disposal
No special requirements.
7
MARKETING AUTHORISATION HOLDER
Farmalider, S.A.
c/ Aragoneses 15
28108, Alcobendas-Madrid
Spain
8
MARKETING AUTHORISATION NUMBER
[To be completed nationally]
9
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
[To be completed nationally]
10
DATE OF REVISION OF THE TEXT
21.06.2013