Source: Medicines Authority (MT) Revision Year: 2022 Publisher: LABORATORIO DE APLICACIONES FARMACODINÁMICAS, S.A. – FARDI, Grassot, 16 – 08025-Barcelona (Spain) <u>Local representative:</u> Europharma Ltd, Catalunya Buildings, Psaila Street, Birkirkara. BKR 9076. ...
Algidrin pediatric 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 Algidrin pediatric 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.
Adverse reactions caused by the active substance together and de concomitand use of alcohol use, especially reactions related to the gastrointestinal tract or central nervous system, can be augmented by the use of NSAIDs.
Gastrointestinal haemorrhages, ulcers and perforations: during treatment with NSAIDs, which include ibuprofen, reports have been received of gastrointestinal haemorrhages, ulcers and perforations (which may be fatal) at any time, with or without prior symptoms of alert and with or without a previous history of severe gastrointestinal events.
The risk of gastrointestinal haemorrhage, ulcer or perforation is higher with increasing doses of NSAIDs, in patients with a history of ulcer, especially if the ulcers were complicated by haemorrhage or perforation (see section 4.3), and in elderly patients. These patients should begin treatment with the lowest possible dose. They should be prescribed concomitant treatment with protective agents (e.g. misoprostol or proton pump inhibitors); combined treatment should also be considered for patients who require low doses of acetylsalicylic acid or other medicinal products that could increase gastrointestinal risk factors (see below and section 4.5).
Patients with a history of gastrointestinal toxicity, and especially elderly patients, should be advised to consult a physician immediately in the event of infrequent abdominal symptoms (especially gastrointestinal bleeding) during treatment and especially during the initial stages.
Special precaution is recommended for patients who receive concomitant treatments that could increase the risk of gastrointestinal ulcer or bleeding such as dicoumarin-based oral anticoagulants or antiplatelet agents such as acetylsalicylic acid (see section 4.5). Furthermore, certain precaution should be taken with the concomitant administration of oral corticosteroids and selective serotonin reuptake inhibitor antidepressants (SSRI).
Treatment should be stopped immediately if gastrointestinal haemorrhage or ulcer occur in patients under treatment with this medicinal product (see section 4.3).
NSAIDs should be administered with precaution in patients with a history of ulcerative colitis or Crohn’s disease, as they could exacerbate these conditions (see section 4.8).
Special caution should be taken in patients with a history of high blood pressure and/or heart failure as fluid retention and oedema have been associated with NSAID treatments.
Clinical trials suggest that the use of ibuprofen, especially at high doses (2,400 mg/day) could be associated with a small increase in the risk of arterial thrombotic events (for example, myocardial infarction or stroke). In general, epidemiological studies do not suggest that ibuprofen at low doses (e.g. ≤ 1,200 mg/day) is associated with increased risk of arterial thrombotic events.
Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischaemic heart disease, peripheral artery disease and/or cerebrovascular disease should only be treated with ibuprofen after careful assessment and avoiding high doses (2,400 mg/day).
Careful assessment should also be applied before starting long-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, smokers), especially if they require high doses of ibuprofen (2,400 mg/day).
Very rare reports have been received of severe skin reactions, some fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis in association with the use of NSAIDs (see section 4.8). Patients appear to be most at risk of suffering these reactions at the start of treatment: in most cases these adverse reactions appear during the first month of treatment. Acute generalised exanthematous pustulosis (AGEP) has been reported in relation to ibuprofencontaining products. Administration of the medicinal product should be immediately stopped at the first symptoms of cutaneous erythema, mucosal lesions or other signs of hypersensitivity.
On exceptional occasions, chicken pox can cause skin and soft tissue infectious complications. To date, the role of NSAIDs in exacerbating these infections cannot be excluded. Therefore ibuprofen should be avoided in cases of chicken pox.
Severe acute hypersensitivity reactions (e.g. anaphylactic shock) have been observed on very rare occasions. Treatment should be stopped when the first signs of a hypersensitivity reaction appear after taking/administering ibuprofen.
Necessary medical measures, in accordance with the symptoms, should be started by specialist personnel. Precaution is required in patients who have suffered hypersensitivity or allergic reactions to other substances, as this can increase the risk of hypersensitivity reactions with ibuprofen.
Precaution is required in patients who suffer seasonal allergies, nasal polyps or chronic obstructive breathing disorders, as there is a high risk of allergic reactions occurring. These reactions may present as asthma attacks, Quincke’s oedema or urticaria.
Ibuprofen should be used with precaution in patients with liver or kidney disease, especially during simultaneous treatment with diuretics, as the resulting prostaglandin inhibition can produce fluid retention and impair kidney function. If administered to these patients, the dose of ibuprofen should be as low as possible and kidney function should be regularly monitored.
There is a risk of kidney impairment in children, adolescents and dehydrated elderly patients. In the event of dehydration, ensure sufficient liquid intake. Special precaution should be taken in children with severe dehydration, for example due to diarrhoea, as dehydration could act as a trigger factor for developing kidney failure.
In general, habitual use of analgesics, especially the combination of different analgesic substances, can produce lasting kidney injuries, with a risk of kidney failure (analgesic nephropathy).
As other NSAIDs, long-term treatments with ibuprofen can cause renal papillary necrosis and other kidney diseases. Renal toxicity has also been observed in patients whose renal prostaglandins play a compensatory role in renal perfusion. Elderly patients, patients with kidney failure, heart failure, liver dysfunction and those being treated with diuretics or antihypertensives (ACE inhibitors) have a high risk of suffering this reaction. Stopping therapy with NSAIDs normally re-establishes the pre-treatment state.
As with other NSAIDs, ibuprofen can produce mild transitory increases in certain liver parameters and significant increases in SGOT and SGPT levels. Treatment should be suspended in the event of a significant increase in these parameters (see sections 4.2 and 4.3).
Elderly patients suffer a higher incidence of adverse reactions to NSAIDs, specifically gastrointestinal haemorrhages and perforations, which can be fatal (see section 4.2).
As with other NSAIDs, anaphylactic/anaphylactoid reactions can occur without previous exposure to the drug. It should also be used with precaution in patients with a history of bronchial asthma, chronic rhinitis or allergic diseases, as cases of bronchospasm, urticaria and angioedema have been reported in this type of patients (see section 4.3).
On rare occasions, cases of aseptic meningitis have been reported with the use of ibuprofen. In most cases, the patients suffered from some form of autoimmune disease (such as systemic lupus erythematosus or other connective tissue diseases), which represented a risk factor, although cases in patients with no chronic disease have also been reported (see section 4.8). The observed symptoms of aseptic meningitis were stiff neck, headache, nausea, vomiting, fever and disorientation.
Special medical control is required during administration in patients immediately after undergoing major surgery.
Like other NSAIDs, it should only be used after strict assessment of the risk/benefit in patients with acute intermittent porphyria.
Kidney function, liver function, haematological function and blood counts should be checked as a precautionary measure in patients on long-term treatment, as ibuprofen, like other NSAIDs, can inhibit platelet aggregation and prolong bleeding time.
Adverse reactions can be minimised using the minimum effective dose for as short a time as possible.
This medicinal product can produce allergic reactions because it contains Allura Red AC dye (E129). It may cause asthma, especially in patients allergic to acetylsalicylic acid.
This medicinal product contains Maltitol (E-965) and each ml of suspension contains 25 mg of sorbitol (E-420). Patients with hereditary fructose intolerance should not take this medicinal product.
This medicinal product contains methyl para-hydroxybenzoate (E-218), ethyl parahydroxybenzoate (E-214) and propyl para-hydroxybenzoate (E-216) and may produce allergic reactions (possibly delayed).
Interference with analytical tests:
Bleeding time (may be prolonged for 1 day after suspending treatment).
Blood sugar levels (may be reduced).
Creatinine clearance (may be reduced).
Haematocrit or haemoglobin levels (may be reduced).
Concentrations of blood urea nitrogen and serum concentrations of creatinine and potassium (may be increased).
Liver function tests: raised transaminase values.
In general, NSAIDs should be used with precaution when used with other drugs that could increase the risk of gastrointestinal ulceration, gastrointestinal haemorrhage and kidney dysfunction.
Interactions have been reported with the following medicinal products:
1) First and second trimester of pregnancy
Prostaglandin synthesis inhibition negatively affects pregnancy and/or development of the embryo/foetus. Data from epidemiological studies suggest an increase of the risk of miscarriage and heart malformations and gastroschisis after the use of a prostaglandin synthesis inhibitor in the early stages of pregnancy. The absolute risk of heart malformations increased from less than 1% to approximately 1.5%. The risk seems to increase with the dose and duration of treatment.
In animals, administration of a prostaglandin synthesis inhibitor has been shown to produce an increase in pre and post-implantation losses and embryo/foetal mortality. There have also been reports of increased incidence of different malformations, including cardiovascular malformations, in animals administered a prostaglandin synthesis inhibitor during the organogenic period.
From the 20th week of pregnancy onward, ibuprofen 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, ibuprofen should not be administered during the first and second trimester of pregnancy unless considered strictly necessary. If ibuprofen is to be used in a woman trying to become pregnant, or during the first and second trimester of pregnancy, the dose and duration of the treatment should be reduced as much as possible. Antenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to ibuprofen for several days from gestational week 20 onward. Ibuprofen should be discontinued if oligohydramnios or ductus arteriosus constriction are found.
2) Third trimester of pregnancy
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose:
Consequently, ibuprofen is contraindicated during the third trimester of pregnancy (see sections 4.3 and 5.3).
Ibuprofen and its metabolites enter breast milk at low concentrations. To date, no harmful effects to infants have been found, so in general breast-feeding does not need to be stopped during shortterm treatment at the recommended dose for pain and fever.
The use of ibuprofen may alter feminine fertility and is not recommended in women who are trying to become pregnant. Women with conception difficulties or who are undergoing fertility testing should consider suspending this medicinal product.
Patients who experience dizziness, vertigo, visual alterations or other disorders of the central nervous system while taking ibuprofen should avoid driving or handling machinery.
Patients in treatment with ibuprofen may find their reaction times affected, which should be borne in mind when performing activities that require greater attention, such as driving or using machinery.
This effect is heightened by simultaneous consumption of alcohol.
The adverse reactions observed with greatest frequency are of gastrointestinal nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, in some cases fatal, may occur, especially in the elderly (see section 4.4). Reports have also been received of nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerous stomatitis and exacerbation of colitis and Crohn’s disease (see section 4.4). The appearance of gastritis has been observed less frequently.
Adverse reactions are presented by organ or system and frequency according to the following classification: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known frequency (cannot be estimated from the available data).
The frequencies given below refer to short-term use at the maximum daily doses of 1,200 mg of oral ibuprofen.
Common: dyspepsia, diarrhoea, nausea, vomiting, abdominal pain, flatulence, constipation, melena, haematemesis, gastrointestinal haemorrhage.
Uncommon: gastritis, duodenal ulcer, gastric ulcer, mouth ulcer, gastrointestinal perforation.
Very rare: pancreatitis.
Not known frequency: exacerbation of colitis, Crohn’s disease.
Uncommon: skin rash, urticaria, itching, purpura (including allergic purpura), photosensitivity reaction.
Very rare: bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, erythema multiforme. Severe skin infections and soft tissue complications during chicken pox may exceptionally appear (see also ‘Infections and Infestations’ and section 4.4).
Not known frecuency: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Acute generalised exanthematous pustulosis (AGEP).
Uncommon: rhinitis.
Rare: aseptic meningitis (see section 4.4).
Uncommon: Hypersensitivity2.
Rare: Anaphylactic reaction: the symptoms may include swelling of the face, tongue and larynx, dyspnoea, tachycardia, hypotension (anaphylaxis, angioedema or severe shock).
Common: headache, dizziness.
Uncommon: paraesthesia, drowsiness.
Rare: optic neuritis.
Infrequent: insomnia, anxiety.
Rare: depression, confusion, disorientation.
Uncommon: hearing disorders.
Rare: vertigo, tinnitus.
Uncommon: visual alterations.
Rare: reversible toxic amblyopia.
Uncommon: asthma, bronchospasm, dyspnoea.
Rare: thrombocytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolytic anaemia. The initial symptoms are: fever, sore throat, superficial mouth ulcers, flulike symptoms, extreme tiredness, and nose and skin bleeding of unknown cause.
Very rare: heart failure, myocardial infarction (see section 4.4).
Very rare: hypertension.
Uncommon: hepatitis, jaundice, liver dysfunction.
Rare: liver failure.
Very rare: liver failure.
Uncommon: interstitial nephritis, nephrotic syndrome and kidney failure, acute kidney failure, papillary necrosis (especially with prolonged use) associated with an increase in urea.
Common: fatigue.
Rare: oedema.
1 Infections and infestations: Exacerbation of infection-related inflammations (e.g. necrotising fasciitis) have been reported coinciding with the use of NSAIDs. Medical attention should be sought as soon as possible if there are signs or worsening of infection when using ibuprofen.
2 Hypersensitivity: Hypersensitivity reactions have been observed after treatment with NSAIDs. These may consist of: (a) a non-specific allergic respiratory tract and anaphylaxia; (b) reactivity of the respiratory tract such as asthma, aggravated asthma, bronchospasm or dyspnoea; or (c) various alterations to the skin, including rash of various types, itching, purpura, angioedema and, on very rare occasions, erythema multiforme and dermatosis (including Stevens-Johnson syndrome, epidermal toxic necrosis).
3,4 Heart and vascular disorders: Clinical trials suggest that the use of ibuprofen, especially at high doses (2,400 mg a day) could be associated with a small increase in the risk of arterial thrombotic events (such as myocardial infarction or stroke, see section 4.4).
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 ADR Reporting Website: www.medicinesauthority.gov.mt/adrportal.
Not applicable.
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