Ibuprofen/Pseudoephedrine Hydrochloride 100mg/15mg Per 5 Ml Oral Suspension
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Ibuprofen/Pseudoephedrine hydrochloride 100mg/15mg per 5ml Oral suspension
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
5ml of suspension contains 100mg of ibuprofen and 15 mg of pseudoephedrine hydrochloride.
Excipients with known effect:
Maltitol, sodium methyl parahydroxybenzoate and sodium propyl parahydroxybenzoate.
For the full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Oral suspension.
A sugar free suspension, white in colour with cherry flavouring.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Ibuprofen/Pseudoephedrine hydrochloride is effective in the relief of feverishness and symptoms of colds and influenza with associated congestion, including aches and pains, headache, sore throat, blocked nose and sinuses.
4.2 Posology and method of administration
This combination product should be used where 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
Adults, older people and adolescents aged 15 years and above:
The usual recommended dose is depending on the severity of symptoms 10ml to 20ml every four to six hours. Leave at least four hours between each dose and do not take more than 60ml 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.
Older people :
No special dosage modifications are required, unless renal or hepatic function is impaired, in which case dosage should be assessed individually.
In older people 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/Pseudoephedrine hydrochloride is contraindicated in children less than 15 years old (see section 4.3).
If in adolescents over 15 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.
Method of administration
For oral administration and for short term use only.
4.3 Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs;
Children less than 15 years old (see section 4.3);
Active or previous peptic ulcer. History of upper gastrointestinal bleeding or perforation, related to previous NSAIDs therapy;
Use with concomitant NSAIDs including cyclo-oxygenase-2 specific inhibitors (see section 4.5);
Concomitant use of:
o Monoamine oxidase inhibitors (MAOIs, or within 14 days of stopping treatment, see section 4.5),
o Beta-blockers (see section 4.5),
o oral anticoagulants,
o corticosteroids,
o heparins at curative doses or in the elderly, o anti-platelet agents,
o lithium,
o selective serotonin reuptake inhibitors (SSRIs),
o methotrexate (used at doses higher than 20 mg /week), o other sympathomimetic decongestants;
• Cardiovascular disease including hypertension
o severe heart failure (NYHA Class IV),
o coronary arterial disease,
o history of myocardial infarction;
• History of stroke or presence of risk factors for stroke (because of the a-sympathomimetic activity of pseudoephedrine hydrochloride);
• Diabetes mellitus;
• Hyperthyroidism;
• Phaeochromocytoma;
• Closed angle glaucoma;
• Prostatic enlargement;
• Severe renal failure;
• Hepatic failure;
• Pregnancy and lactation;
• Cerebrovascular or other bleeding;
• Unexplained haematopoietic abnormalities;
• History of seizures;
• Disseminated lupus erythematosus
4.4 Special warnings and precautions for use
Concomitant use of Ibuprofen/Pseudoephedrine hydrochloride 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 15 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/Pseudoephedrine 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/Pseudoephedrine hydrochloride is taken concomitantly with other medicines containing vasoconstrictors.
Patients with urethroprostatic disorders are more prone to develop symptoms like dysuria and urinary retention.
Older 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/Pseudoephedrine 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.
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/Pseudoephedrine may precipitate an acute asthma attack; particularly in some patients who are allergic to acetylsalicylic acid or an NSAID (see section 4.3).
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/Pseudoephedrine 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.
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 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/Pseudoephedrine should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Precautions for use related to ibuprofen:
• Older people: 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.
This medicinal product contains:
- maltitol liquid. Patients with rare hereditary problems of fructose intolerance
should not take this medicine.
- sodium methyl parahydroxybenzoate (E219) and sodium propyl
parahydroxybenzoate (E217). These may cause allergic reactions (possibly delayed).
less than 1 mmol sodium (23 mg) per dose of 10 ml, i.e. essentially ‘sodium- free’.
4.5 Interaction with other medicinal products and other forms of interaction
|
Combination of |
Possible Reaction |
|
pseudoephedrine with: |
|
Non-selective monoamine oxidase inhibitors (MAOIs): |
Ibuprofen/Pseudoephedrine hydrochloride 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 sympathomimetics 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/Pseudoephedrine hydrochloride 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 several 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, 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). |
|
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/Pseudoephedrine hydrochloride 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/Pseudoephedrine hydrochloride 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, betareceptor-blockers 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, betareceptor-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/Pseudoephedrine hydrochloride and potassium-sparing diuretics may lead to hyperkalaemia (check of serum potassium is recommended). |
|
Methotrexate: |
The administration of Ibuprofen/Pseudoephedrine hydrochloride 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 antiinflammatory 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. |
4.6 Fertility, Pregnancy and lactation
Pregnancy
Whilst no teratogenic effects have been demonstrated with ibuprofen in animal experiments, there is a possible association between the development of foetal abnormalities and exposure to pseudoephedrine in the first trimester. The use of Ibuprofen/Pseudoephedrine during pregnancy should, therefore, be avoided.
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. (See section 4.3 Contraindications).
Breast- feeding
Although ibuprofen appears in breast milk in very low concentrations, significant amounts of pseudoephedrine are secreted into breast milk. The use Ibuprofen/Pseudoephedrine during lactation should, therefore, be avoided.
Fertility
Impaired female 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/Pseudoephedrine hydrochloride 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
(c) 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 (2400mg/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/Pseudoephedrine 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 |
Ibuprofen |
Very rare |
Exacerbation of infectious |
|
and |
inflammations (e.g. necrotizing | ||
|
infestations |
fasciitis), aseptic meningitis |
|
(stiffness of the neck, 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 asthma attacks (with drop in blood pressure) |
|
Ibuprofen and pseudoephedrin e 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 |
Very rare |
Psychotic reactions, depression |
|
Pseudoephedrin e hydrochloride |
Not known |
Agitation, hallucination, anxiety, abnormal behaviour, insomnia | |
|
Nervous system disorders |
Ibuprofen |
Uncommon |
Central nervous disturbances such as headache, dizziness, sleeplessness, agitation, irritability or tiredness |
|
Pseudoephedrin e hydrochloride |
Rare Not known |
Insomnia, nervousness anxiety, restlessness, tremor, hallucinations Haemorhagic stroke, ischemic stroke, convulsion, headache | |
|
Eye disorders |
Ibuprofen |
Uncommon |
Visual disturbances |
|
Ear and labyrinth disorders |
Ibuprofen |
Rare |
Tinnitus |
|
Cardiac disorders |
Ibuprofen |
Very rare |
Oedema, hypertension, palpitations, heart failure, myocardial infarction |
|
Pseudoephedrin e hydrochloride |
Not known |
Palpitations, tachycardia, chest pain, arrhythmia | |
|
Vascular disorders |
Ibuprofen |
Very rare |
Arterial hypertension |
|
Pseudoephedrin e hydrochloride |
Not known |
Hypertension | |
|
Respiratory, thoracic and mediastinal disorders |
Pseudoephedrin e hydrochloride |
Rare |
Exacerbation of asthma or hypersensitivity reaction with bronchospasm |
|
Gastrointest inal 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, ulcerous stomatitis. Exacerbation of colitis and Crohn’s disease (see section 4.4) | |
|
Ibuprofen |
Very rare |
Oesophagitis, pancreatitis, intestinal diaphragm-like stricture | |
|
Pseudoephedrin e hydrochloride |
Not known |
Dry mouth, thirst, nausea, vomiting | |
|
Hepatobiliar y disorders |
Ibuprofen |
Very rare |
Hepatic dysfunction, hepatic damage, particularly in long-term therapy, hepatic failure, acute hepatitis |
|
Skin and subcutaneou s 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 | |
|
Pseudoephedrin e hydrochloride |
Not known |
Rash, urticaria, pruritus, erythema, hyperhidrosis |
|
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 | |
|
Pseudoephedrin e 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 at: www.mhra.gov.uk/yellowcard
4.9 Overdose
Paediatric population
In children, ingestion of more than 400mg/kg ibuprofen may cause symptoms. In adults, the dose response is less clear cut. 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 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.
Other symptoms of overdosage which may be associated with pseudoephedrine include anxiety, restlessness, irritability, fever, sinus tachycardia, sweating, insomnia, dilated pupils, blurred vision, delusions and hallucinations, muscular weakness, difficulty in micturition, tremors, convulsions, coma, respiratory depression, hypertension, supraventricular and ventricular arrhythmias.
Management
Management should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable. Consider oral administration of activated charcoal if the patient presents within 1 hour of ingestion of a potentially toxic amount. If frequent or prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.
Chlorpromazine may be used to control marked excitement and hallucinations. Severe hypertension may need to be treated with an alpha-receptor blocking drug such as phentolamine. A beta-receptor blocking drug may be required to control cardiac arrhythmias.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: other cold combination preparations, ATC code: R05X
Ibuprofen is a propionic acid derivative, having analgesic, anti-inflammatory and antipyretic activity. The drug’s therapeutic effects as a non-steroidal antiinflammatory drug are thought to result from inhibitory activity on prostaglandin synthesis. Furthermore, ibuprofen reversibly inhibits 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).
Pseudoephedrine is a sympathomimetic agent with direct and indirect effects on adrenergic receptors. It has alpha and beta stimulant adrenergic activity and some stimulant effect on the central nervous system. The sympathomimetic effect of Pseudoephedrine produces vasoconstriction, which in turn relieves nasal congestion.
5.2 Pharmacokinetic properties
Ibuprofen is rapidly absorbed from the gastrointestinal tract and is rapidly distributed throughout the whole body. Peak serum concentrations occur 1-2 hours after administration. The elimination half-life is approximately two hours.
Ibuprofen is metabolised in the liver to two major inactive metabolites and the
kidney excretes these together with unchanged ibuprofen either as such or as conjugated. Excretion by the kidney is both rapid and complete.
Ibuprofen is extensively bound to plasma proteins.
Pseudoephedrine is absorbed from 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
No relevant information additional to that contained elsewhere in the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Glycerol
Xanthan Gum
Maltitol Liquid
Polysorbate 80
Saccharin Sodium
Citric Acid Monohydrate
Sodium Methyl Parahydroxybenzoate (E219)
Sodium Propyl Parahydroxybenzoate (E217)
Cherry Flavour (K11181)
Consisting of: propylene glycol, water, flavouring substances + flavouring preparations, trisodium citrate buffer.
Purified Water
6.2 Incompatibilities
Not applicable
6.3 Shelf life
2 years
After first opening: 3 months
6.4 Special precautions for storage
Do not store above 25°C.
Store in the original container in order to protect from light.
6.5 Nature and contents of container
Amber Type III Glass
Child Resistant Tamper Evident Cap (High density polypropylene cap with a polyethylene lining)
2.5ml/ 5ml Polypropylene double ended spoon Pack-sizes:
1 bottle of 100ml and a double-ended 5ml and 2.5ml polypropylene spoon is also included to help measure the dose.
6.6 Special precautions for disposal
Not applicable
7 MARKETING AUTHORISATION HOLDER
Boehringer Ingelheim International GmbH Binger StraBe 173,
55216 Ingelheim am Rhein,
Germany
8 MARKETING AUTHORISATION NUMBER(S)
PL 14598/0103
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
23/09/2014 09/11/2016