Summary of medicine characteristics - IBUPROFEN AND PSEUDOEPHEDRINE HYDROCHLORIDE FARMALDIER 200 MG / 30 MG / 10ML ORAL SUSPENSION
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen and Pseudoephedrine hydrochloride Farmalider 200 mg/ 30 mg/10 ml oral suspension
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml of oral suspension contains:
Ibuprofen
Pseudoephedrine hydrochloride
Excipients with known effect:
Glycerol (E-422)
Maltitol..........................................500 mg
Sodium...........................................2.68 mg
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Oral suspension.
A white color suspension with orange flavouring.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the relief of symptoms of cold and flu with associated pain, fever, congestion and blocked nose.
Ibuprofen and Pseudoephedrine hydrochloride Farmalider is indicated in adults and adolescents over 12 years of age.
4.2 Posology and method of administration
This combination product should be used when both, the decongestant action of Pseudoephedrine hydrochloride and the analgesic and/or anti-inflammatory and/or antipyretic action of Ibuprofen, are required. If one symptom (either nasal congestion or headache and/or fever) predominates, single-agent therapy is preferable.
Posology
The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see section 4.4).
Adults, the elderly and adolescents over 12 years:
The usual recommended dose is depending on the severity of symptoms 10 ml to 20 ml every six to eight hours. Leave at least four hours between each dose and do not take more than 60 ml in 24 hours.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
The adult patient should consult a doctor if symptoms persist or worsen or if the product is required for more than 5 days.
Elderly:
No special dosage modifications are required, unless renal or hepatic function is impaired, in which case dosage should be assessed individually.
In elderly and patients with a history of ulcers, particularly if complicated by haemorrhage or perforation (see section 4.3), start with lowest dose possible as the risk of gastrointestinal haemorrhage, ulceration or perforation is higher with increased doses of NSAIDs.
The concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients or patients taking other drugs that can increase the risk of gastrointestinal events (see below and section 4.5).
Paediatric population:
Ibuprofen and Pseudoephedrine hydrochloride Farmalider is contraindicated in children under the age of 12 (see section 4.3).
If in adolescents over 12 years this medicinal product is required for more than 3 days, or if symptoms worsen a doctor should be consulted.
Parents or carers should seek medical attention if the child’s condition deteriorates during treatment. Do not exceed the stated dose.
The maximum total daily dose of 60 ml (equivalent to 1200 mg of ibuprofen and 180 mg of pseudoephedrine hydrochloride) should not be exceeded.
Method of administration
For oral administration only.
4.3 Contraindications
Hypersensitivity to ibuprofen, pseudoephedrine or to any of the excipients listed in section 6.1.
Use in children under 12 years of age.
Patients with allergy to aspirin or other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or with a history of hypersensitivity reactions (e.g. asthma, bronchospasm, rhinitis, angioedema or urticarial) in response to ibuprofen, aspirin or NSAIDs.
During pregnancy (see section 4.6).
History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
Cerebrovascular or other bleeding.
Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Patients with phaeochromocytoma, closed angle glaucoma, diabetes or thyroid disease.
Patients with history of haemorrhagic stroke.
Patients suffering from heart disease, circulatory problems, prostatic hypertrophy, hypertension, coronary artery disease, angina pectoris, tachycardia or haemorrhagic diathesis.
Patients taking other NSAIDs including cyclooxygenase-2 selective inhibitors, pain-relievers or decongestants.
Patients receiving tricyclic antidepressants.
Patients with severe heart failure (NYHA Class IV), renal failure or hepatic failure (see section 4.4).
History of seizures.
Unexplained haematopoietic abnormalities.
Disseminated lupus erythematosus.
History of stroke or presence of risk factors for stroke.
Concomitant use of monoamine oxidase inhibitors (MAOIs, or within 14 days of stopping treatment, see section 4.5).
Concomitant use of other vasoconstrictor drugs used as nasal decongestants, whether administered orally or nasally (e.g. phenylpropanolamine, phenylephrine and ephedrine), and methylphenidate (see section 4.5).
Risk of urinary retention associated with uretroprostatic disorders.
4.4 Special warnings and precautions for use
Concomitant use of Ibuprofen and Pseudoephedrine hydrochloride Farmalider with other NSAIDs containing cyclo-oxygenase (COX)-2 inhibitors should be avoided.
Undesirable effects may be reduced by using the minimum effective dose for the shortest duration necessary to control symptoms (see „Gastro-intestinal effects“ and „Cardiovascular and cerebrovascular effects“ below).
Special warnings related to pseudoephedrine hydrochloride:
The dosage, the recommended maximum duration of treatment (5 days; in adolescents aged 12 years and above, 3 days) and the contraindications must be strictly adhered to (see section 4.8).
Patients should be informed that treatment must be discontinued if they develop hypertension, tachycardia, palpitations, cardiac arrhythmias, nausea or any neurological signs such as onset or worsening of headache.
Before using this product, patients should consult their doctor in case of:
Hypertension, heart disease, hyperthyroidism, psychosis or diabetes.
Concomitant administration of antimigraine agents, especially ergot alkaloid vasoconstrictors (because of the a-sympathomimetic activity of pseudoephedrine).
Systemic lupus erythematosus and mixed connective tissue disease -increased risk of aseptic meningitis (see section 4.8).
Neurological symptoms such as seizures, hallucinations, behavioural disturbances, agitation and insomnia have been described after systemic administration of vasoconstrictors, especially during febrile episodes or on overdose. These symptoms have been more commonly reported in paediatric population.
As a result, it is advisable:
to avoid administration of Ibuprofen and Pseudoephedrine hydrochloride Farmalider either in combination with medicines which can lower the epileptogenic threshold, such as terpene derivatives, clobutinol, atropine-like substances and local anaesthetics, or where there is a history of seizures.
to adhere strictly to the recommended dosage in all cases and to inform the patients about the risks of overdose if Ibuprofen and Pseudoephedrine hydrochloride Farmalider is taken concomitantly with other medicines containing vasoconstrictors.
Patients with urethroprostatic disorders are more prone to develop symptoms like dysuria and urinary retention.
Elderly patients may be more sensitive to the effects on the central nervous system (CNS).
Precautions for use related to pseudoephedrine hydrochloride:
In patients undergoing scheduled surgery in which volatile halogenated anaesthetics are to be used, it is preferable to discontinue treatment with Ibuprofen and Pseudoephedrine hydrochloride Farmalider several days before surgery in view of the risk of acute hypertension (see section 4.5).
Athletes should be informed that treatment with pseudoephedrine hydrochloride can lead to positive results in doping tests.
Interference with serological testing
Pseudoephedrine has the potential to reduce iobenguane i-131 uptake in neuroendocrine tumors, thus interfering with scintigraphy.
Ischaemic colitis
Some cases of ischaemic colitis have been reported with pseudoephedrine. Pseudoephedrine should be discontinued and medical advice sought if sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis develop.
Ischaemic optic neuropathy
Cases of ischaemic optic neuropathy have been reported with pseudoephedrine. Pseudoephedrine should be discontinued if sudden loss of vision or decreased visual acuity such as scotoma occurs.
Special warnings related to ibuprofen:
Bronchospasm may be precipitated in patients suffering from, or with a history of bronchial asthma or allergic disease. The product should not be taken in case of asthma without prior consultation with a doctor (see section 4.3).
Patients who have asthma associated with chronic rhinitis, chronic sinusitis and/or nasal polyposis have a higher risk of allergic reactions when taking acetylsalicylic acid and/or NSAIDs. Administration of Ibuprofen and Pseudoephedrine hydrochloride Farmalider may precipitate an acute asthma attack; particularly in some patients who are allergic to acetylsalicylic acid or an NSAID (see section 4.3).
There is a risk of renal failure in dehydrated adolescents.
Gastro-intestinal effects:
Gastro-intestinal 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 gastrointestinal events.
The risk of gastro-intestinal bleeding, ulceration or perforation, which can be fatal, is higher with increasing NSAID doses, in patients with a history of ulcer (particularly if complicated with bleeding or perforation (see section 4.3) and in patients older than 60 years of age. 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 taking concomitant low-dose acetylsalicylic acid or other medicinal drug products likely to increase gastro-intestinal risk (see below and section 4.5).
Patients with a history of gastrointestinal toxicity, especially elderly patients, may present with unusual abdominal symptoms (especially gastrointestinal bleeding) in the initial stages of treatment.
Particular caution is advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding such as oral corticosteroids, anticoagulants such as warfarin, SSRIs or antiplatelet agents such as acetylsalicylic acid (see section 4.5).
Treatment with Ibuprofen and Pseudoephedrine hydrochloride Farmalider should be discontinued immediately if gastro-intestinal bleeding or ulceration occurs.
NSAIDs should be given with care to patients with a history of gastro-intestinal disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated (see section 4.8).
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.
Cardiovascular and cerebrovascular effects:
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.
Caution is required in patients with a history of hypertension and/or heart failure as fluid retention, hypertension or oedema have been observed in association with previous NSAID therapy; advice from a doctor and/or pharmacist must be sought prior to starting treatment under these circumstances.
Severe skin reactions:
Severe skin reactions such as acute generalised exanthematous pustulosis (AGEP) may occur with ibuprofen and pseudoephedrine-containing products. 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 NSAIDs (see section 4.8). Patients are at highest risk of 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 and Pseudoephedrine hydrochloride Farmalider should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Masking of symptoms of underlying infections
Ibuprofen and Pseudoephedrine hydrochloride Farmalider 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 and Pseudoephedrine hydrochloride Farmalider 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.
Precautions for use related to ibuprofen:
Elderly: the pharmacokinetics of ibuprofen is not modified by age, no dose adjustments is necessary in the older population. However, elderly patients should be carefully monitored as they are more sensitive to NSAID-related undesirable effects, particularly gastro-intestinal bleeding and perforation, which can be fatal.
Caution and special monitoring is required when administering ibuprofen to patients with a history of gastro-intestinal disease (such as peptic ulcer, hiatus hernia or gastrointestinal bleeding).
In the initial stages of treatment, careful monitoring of urine output and renal function is required in patients with heart failure, patients with chronically impaired renal or hepatic function, patients taking diuretics, patients who are hypovolaemic as a result of major surgery and, in particular, elderly patients. Renal function in these patients may be adversely influenced by treatment with NSAIDs.
If visual disturbances occur during the course of treatment, a full ophthalmological examination should be carried out.
If symptoms persist or worsen, the patient should consult a doctor.
Warnings about excipients
This medicinal product contains glycerol, it may cause headache, stomach upset and diarrhoea.
This medicinal product contains maltitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
This medicinal product contains 1.17 mmol (26.8 mg) sodium per dose (10 ml). To be taken into consideration by patients on a controlled sodium diet.
4.5 Interaction with other medicinal products and other forms of interaction
| Combination of pseudoephedrine with: | Possible Reaction |
| Non-selective monoamine oxidase inhibitors (MAOIs): | Ibuprofen and Pseudoephedrine hydrochloride Farmalider must not be taken by patients taking monoamine oxidase inhibitors (MAOIs) currently or in the last two weeks, since there is a risk of hypertensive episodes as paroxysmal hypertension and hyperthermia, which can be fatal (see section 4.3). |
| Other indirectly-acting, orally or nasally administered sympathomimetic or vasoconstrictor agents, a- sympathomimetic drugs, phenylpropanolamine, phenylephrine, ephedrine, methylphenidate: | Pseudoephedrine may potentiate the effect of other sympathomimetic (vasoconstrictor) and lead to risk of vasoconstriction and/or hypertensive crises. |
| Reversible inhibitors of monoamine oxidase A (RIMAs), linezolid, dopaminergic ergot alkaloids, vasoconstrictor ergot alkaloids: | Risk of vasoconstriction and/or hypertensive crises. |
| Volatile halogenated anaesthetics: | Perioperative acute hypertension. In scheduled surgery, discontinue treatment with Ibuprofen and Pseudoephedrine |
| hydrochloride Farmalider several days before. | |
| Guanethidine, reserpine and methyldopa: | Effect of pseudoephedrine may be diminished. |
| Tricyclic antidepressants: | Effect of pseudoephedrine may be diminished or enhanced. |
| Digitalis, chinidine or tricyclic antidepressants: | Increased frequency of arrhythmia. |
| Concomitant use of ibuprofen with: | Possible Reaction |
| Other NSAIDs, salicylates, analgesics, antipyretics and COX 2: | The concomitant administration of two or more NSAIDs, analgesics, antipyretics and COX 2 selective inhibitors may increase the risk of adverse reactions as gastrointestinal ulcers and bleeding due to a synergistic effect. The concomitant use of with these products should therefore be avoided (see section 4.4). |
| Cardiac glycosides (as digoxin): | The concomitant use with digoxin preparations may increase serum levels cardiac glycosides (digoxin). A check of serum-digoxin is not as a rule required on correct use (maximum over 5 days). |
| Corticosteroids: | Corticosteroids as these may increase the risk of adverse reactions, especially of the gastrointestinal tract (gastrointestinal; ulceration or bleeding) (see section 4.3). |
| Anti-platelet agents: | Increased risk of gastrointestinal bleeding (see section 4.4). |
| Acetylsalicylic acid (low dose): | 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, longterm 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). |
| Anticoagulants: (e.g.: warfarin, ticlopidine, clopidogrel, tirofiban, eptifibatide, abciximab, iloprost) | Increased risk of gastrointestinal bleeding as NSAIDs as ibuprofen may enhance the effect of anti-coagulants (see section 4.4). |
| Phenytoin: | The concomitant use of Ibuprofen and Pseudoephedrine hydrochloride Farmalider with phenytoin preparations may increase serum levels of these medicinal products. A check of serum-phenytoin levels is not as a rule required on correct use (maximum over 5 days) |
| Selective serotonin reuptake inhibitors (SSRIs): | Increased risk of gastrointestinal bleeding (see section 4.4). |
| Lithium: | The concomitant use of Ibuprofen and Pseudoephedrine hydrochloride Farmalider 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 5 days). | |
| Probenecid and sulfinpyrazone: | Medicinal products that contain probenecid or sulfinpyrazone may delay the excretion of ibuprofen. |
| Diuretics, ACE inhibitors, beta-receptorblockers and angiotensin-II antagonists: | NSAIDs may reduce the effect of diuretics and other antihypertensive agents. 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, beta-receptor-blockers or angiotensin-II antagonists and agents that inhibit cyclooxygenase 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 Ibuprofen and Pseudoephedrine hydrochloride Farmalider and potassium-sparing diuretics may lead to hyperkalaemia (check of serum potassium is recommended). |
| Methotrexate: | The administration of Ibuprofen and Pseudoephedrine hydrochloride Farmalider within 24 hours before or after administration of methotrexate may lead to elevated concentrations of methotrexate and an increase in its toxic effect. |
| Ciclosporin: | The risk of a kidney-damaging effect due to ciclosporin is increased through the concomitant administration of certain nonsteroidal anti-inflammatory drugs. This effect also cannot be ruled out for a combination of ciclosporin with ibuprofen. |
| Tacrolimus: | The risk of nephrotoxicity is increased if the two medicinal products are administered concomitantly. |
| 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 anti-inflammatory 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. |
| Heparins; Ginkgo biloba : | Increased risk of bleeding. |
| Mifepristone: | NSAIDs should not be used for 8–12 days after |
| administration of mifepristone as they may reduce the effect of mifepristone. | |
| Antacids: | Certain antacids may increase the gastrointestinal absorption of ibuprofen. This is considered clinically relevant especially during long-term use of ibuprofen. |
| Aminoglycosides : | NSAIDs may decrease the excretion of aminoglycosides and increase their toxicity. |
4.6 Fertility, pregnancy and lactation
Pregnancy
Ibuprofen and Pseudoephedrine hydrochloride Farmalider is contraindicated during pregnancy (see section 4.3).
Ibuprofen:
During the 3rd trimester, ibuprofen is contraindicated as there is a risk of premature closure of the foetal ductus arteriosus with possible persistent pulmonary hypertension. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child.
Pseudoephedrine hydrochloride:
Pseudoephedrine hydrochloride has been used extensively for many years without apparent negative consequences; however, there may be an increased risk in the early stages of gestation due to its vasoconstricting effects.
Breastfeeding
Although ibuprofen appears in breast milk in very low concentrations, significant amounts of pseudoephedrine are secreted into breast milk. The use of Ibuprofen and Pseudoephedrine hydrochloride Farmalider during lactation should, therefore, be avoided except under the supervision of a doctor when the benefit outweighs the risks.
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.
4.7 Effects on ability to drive and use machines
Ibuprofen and Pseudoephedrine hydrochloride Farmalider has no known effects on the ability to drive and use machines.
However, since dizziness or hallucinations may appear in exceptional cases, owing to the presence of pseudoephedrine, anyone intending to drive should take this possibility into account.
4.8 Undesirable effects
The most commonly-observed adverse events related to ibuprofen are gastrointestinal in nature. In general, the risk of development of adverse events (in particular the risk of development of serious gastrointestinal complications) increases with increasing dose and with increasing duration of treatment administration.
Hypersensitivity reactions have been reported following treatment with ibuprofen. These may consist of:
(a) Non-specific allergic reaction and anaphylaxis.
(b) Respiratory tract reactivity comprising of asthma, aggravated asthma, bronchospasm or dyspnoea.
© Assorted skin disorders, including rashes of various types, pruritis, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
In patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue disease) during treatment with ibuprofen, single cases of symptoms of aseptic meningitis, such as stiff neck, headache, nausea, vomiting, fever or disorientation have 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 following list of adverse effects relates to those experienced with ibuprofen and pseudoephedrine hydrochloride at OTC doses, for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse effects may occur.
Patients should be informed that they should stop taking Ibuprofen and Pseudoephedrine hydrochloride Farmalider immediately and consult a doctor if they experience a serious adverse drug reaction.
Adverse reaction frequency is defined using the following convention: 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).
| Infections and infestations | Ibuprofen | Very rare | Exacerbation of infectious inflammations (e.g. necrotizing fasciitis), aseptic meningitis (neck stiffness, headache, nausea, vomiting, |
| fever or disorientation in patients with pre-existent autoimmune diseases (SLE, mixed connective tissue disease) | |||
| Blood and lymphatic system disorders | Ibuprofen | Very rare | Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, agranulocytosis, neutropenia) |
| Immune system disorders | Ibuprofen | Uncommon | Hypersensitivity reactions with urticaria, pruritus, skin rashes and asthmatic attacks (with drop in blood pressure) |
| Ibuprofen and pseudoephedrine hydrochloride | Very rare | Severe generalised hypersensitivity reactions, signs may be facial oedema, angioedema, dyspnoea, bronchospasm, tachycardia, drop in blood pressure, anaphylactic shock | |
| Psychiatric disorders | Ibuprofen | Not known | Psychotic reactions, depression |
| Pseudoephedrine hydrochloride | Not known | Hallucination, abnormal behaviour | |
| Nervous system disorders | Ibuprofen | Uncommon | Central nervous disturbances such as headache, dizziness, sleeplessness, agitation, irritability or tiredness |
| Pseudoephedrine hydrochloride | Rare Not known | Insomnia, nervousness anxiety, restlessness, tremor, hallucinations Haemorhagic stroke, ischemic stroke, convulsion, headache | |
| Eye disorders | Ibuprofen | Uncommon | Visual disturbances |
| Pseudoephedrine hydrochloride | Not known | Ischaemic optic neuropathy | |
| Ear and labyrinth disorders | Ibuprofen | Rare | Tinnitus |
| Cardiac disorders | Ibuprofen | Very rare | Palpitations, heart failure, myocardial infarction |
| Pseudoephedrine hydrochloride | Rare | Palpitations, tachycardia, chest pain, arrhythmia | |
| Vascular disorders | Ibuprofen | Very rare | Arterial hypertension |
| Pseudoephedrine | Not known | Arterial hypertension |
| hydrochloride | |||
| Respiratory, thoracic and mediastinal disorders | Pseudoephedrine hydrochloride | Rare | Exacerbation of asthma or hypersensitivity reaction with bronchospasm |
| Gastrointestinal disorders | Ibuprofen | Common | Gastrointestinal discomfort, dyspepsia, abdominal pain, nausea, vomiting, flatulence, diarrhoea, anorexia, constipation, minor gastrointestinal blood loss in rare cases leading to anaemia |
| Ibuprofen | Uncommon | Peptic ulcer, perforation, or gastrointestinal haemorrhage with melaena or haematememesis, gastritis, stomatitis ulcerative. Exacerbation of colitis and Crohn’s disease (see section 4.4) | |
| Ibuprofen | Very rare | Oesophagitis, pancreatitis, intestinal diaphragm-like stricture | |
| Pseudoephedrine hydrochloride | Uncommon | Dry mouth, thirst, nausea, vomiting | |
| Pseudoephedrine hydrochloride | Not Known | Ischaemic colitis | |
| Hepatobiliary disorders | Ibuprofen | Very rare | Hepatic dysfunction, hepatic damage, particularly in longterm therapy, hepatic failure, acute hepatitis |
| Skin and subcutaneous tissue disorders | Ibuprofen | Uncommon | Various skin rashes |
| Ibuprofen | Very rare | Severe forms of skin reactions as exfoliative dermatitis or bullous exanthema such as Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis (Lyell syndrome), alopecia, severe skin infections, soft-tissue complications in a varicella infection | |
| Ibuprofen | Not Known | Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), photosensitivity reactions | |
| Pseudoephedrine | Rare | Rash, urticaria, pruritus, |
| hydrochloride | erythema, hyperhidrosis | ||
| Pseudoephedrine hydrochloride | Not Known | Acute generalised exanthematous pustulosis (AGEP) | |
| Renal and Urinary disorders | Ibuprofen | Rare | Kidney-tissue damage (papillary necrosis) and elevated uric acid concentrations in the blood |
| Ibuprofen | Very rare | Renal and hepatic disorders, increase in serum creatinine, liver disorders, oedemas (particularly in patients with arterial hypertension or renal insufficiency), nephrotic syndrome, interstitial nephritis, acute renal insufficiency | |
| Pseudoephedrine hydrochloride | Not known | Urinary retention in men with prostatic hypertrophy |
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; website www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
4.9 OverdoseThe clinical effects of this medication overdose are more likely to be due to pseudoephedrine hydrochloride than to ibuprofen. The effects are not always correlated with the dose taken because of the different inter-individual sensitivity with respect to the sympathomimetic properties.
Symptoms
The most frequent manifestations of ibuprofen overdose are abdominal pain, nausea, vomiting, lethargy, thirst, muscle weakness, drowsiness, blurred vision and dizziness. Other effects including headache, tinnitus, CNS depression, convulsions, hypotension, bradycardia, tachycardia, supraventricular and ventricular arrhythmias, and atrial fibrillation, may occur. Metabolic acidosis, coma, acute renal failure, hyperkalemia, apnoea (mainly in young children), respiratory depression, and respiratory failure have been reported rarely. Exacerbation of asthma is possible in asthmatics. In serious poisoning metabolic acidosis may occur.
Symptoms and signs of pseudoephedrine overdose include irritability, insomnia, fever, sweating, anxiety, restlessness, tremor, convulsions, palpitations (sinus arrhythmia), hypertension, dry mouth, and difficulty in urination. Hallucinations have been reported (more likely in children).
Treatment
Treatment of overdose is supportive. Gastric lavage and activated charcoal may be of benefit within 1 hour of ingestion of a potentially toxic amount, and if necessary, correction of serum electrolytes.
Symptomatic and supportive treatment should be undertaken, particularly with regard to the cardiovascular and respiratory systems. For example, severe hypertension may need to be treated with an alpha-receptor blocking drug, whilst a beta-receptor blocking drug may be required to control cardiac arrhythmias. Convulsions may be controlled with intravenous diazepam, while chlorpromazine may be used to control marked excitement and hallucinations.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: pseudoephedrine combinations, ATC code: R01BA52.
Ibuprofen and Pseudoephedrine hydrochloride Farmalider is a medicine consisting of a combination of two active substances: ibuprofen and pseudoephedrine.
Pseudoephedrine is a sympathomimetic agent with direct and indirect effects on adrenergic receptors. It has alpha and beta stimulant adrenergic stimulant activity and some stimulant effect on the central nervous system. The sympathomimetic effect of pseudoephedrine produces vasoconstriction which relieves nasal congestion.
Ibuprofen is an anti-inflammatory analgesic and antipyretic drug belonging to the group of non-steroidal anti-inflammatory drugs. In humans, it has been shown to be effective in reducing the symptoms (pain, fever and swelling) associated with inflammation and influenza. The therapeutic effects of the drug are the result of an inhibitory activity on the prostaglandin synthesis.
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 400mg was taken within 8 h before or within 30 min after immediate release aspirin dosing (81mg), 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
Ibuprofen:
Ibuprofen is rapidly absorbed from the gastrointestinal tract, and its plasma concentrations reach a maximum peak level about 2 hours after administration.
Elimination half-life is approximately 2 hours.
Ibuprofen is metabolised in the liver into two major inactive metabolites and these together with unchanged ibuprofen are excreted by the kidney either as such or as conjugates. Excretion by the kidney is both rapid and complete. Ibuprofen is extensively bound to plasma proteins.
Pseudoephedrine:
Pseudoephedrine is absorbed in the gastrointestinal tract and is largely excreted in the urine unchanged, together with small amounts of a hepatic metabolite.
It has an elimination half-life of several hours, which may be reduced by acidifying the urine.
5.3 Preclinical safety data
5.3 Preclinical safety dataOnly limited toxicity data are available with the drug combination ibuprofen and pseudoephedrine hydrochloride.
Based on different mechanisms of action of ibuprofen (non-steroidal antiinflammatory) and pseudoephedrine hydrochloride (sympathomimetic), a compoundspecific toxicity profile related to the pharmacodynamic activity of the monocompounds was seen in non-clinical toxicity tests following overdosing (pseudoephedrine human data). Accordingly, there were different toxicological target organs, e.g. gastrointestinal lesions for ibuprofen and hemodynamic as well as CNS-effects for pseudoephedrine hydrochloride. Co-administration of ibuprofen and pseudoephedrine hydrochloride did not result in any clinically significant interaction. Therefore, no additive, synergistic and potentiating effects will be expected for the fixed-dose combination (FDC) ibuprofen/pseudoephedrine hydrochloride (200 mg/30 mg) in animals and men at equipotent doses. This is also supported by the absence of competitive metabolic pathways. There is no scientific evidence that the safety margins for the individual drugs will be different for the drug combination.
6.1
List of excipients Sodium benzoate Anhydrous citric acid Sodium citrate Saccharin sodium Sodium chloride Hypromellose Xanthan gum Liquid maltitol Glycerol (E-422) Thaumatin (E-957)
Orange flavour (contains butylated hydroxyanisole (E-320), alpha-tocopherol (E307))
Purified water.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years.
After the first opening the suspension is stable for 3 months.
6.4 Special precautions for storage
It does not require any special storage conditions.
6.5 Nature and contents of container
Amber-coloured PET bottles, of 150 and 200 ml, with child-resistant closure.
It contains a 5 ml dosing syringe (graduated in milliliters).
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
6.6 Special precautions for disposalDisposal of the unused medicinal product and all materials that have been in contact with it should be carried out in accordance with local regulations.