Nurofen Cold and Flu

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For short-term use only.
The lowest effective dose should be used for the shortest duration necessary to
relieve symptoms. The patient should consult a doctor if symptoms persist or
worsen, or if the product is required for more than 10 days.
Adults and children 12 years of age and over: Take 1 tablet every 4 to 6 hours while symptoms persist. If symptoms do not respond to 1 tablet, 2 tablets may be used.
Do not use more than 6 tablets in any 24-hour period unless directed by a doctor.
Method of administration: For oral administration with water.
Paediatric population: Nurofen Cold and Flu is not indicated for children under
12 years old.

For the relief of symptoms cold and flu accompanied by pains, fever and nasal
congestion.

* Hypersensitivity to ibuprofen, pseudoephedrine or any of the excipients in the
product.
* Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, or urticaria) in response to acetylsalicylic acid (aspirin) or other non-steroidal anti-inflammatory drugs.
* Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
* History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
* Severe coronary heart disease and cardiovascular disorders.
* Phaeochromocytoma: Pseudoephedrine should not be used in patients with phaeochromocytoma
* Severe heart failure or hepatic failure.
* Last trimester of pregnancy
* Not to be used in children under the age of 12 years.
* Monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping treatment
* Severe acute or chronic kidney disease/renal failure.
* Severe hypertension or uncontrolled hypertension.

Undesirable effects may be minimized by using the lowest effective dose for the shortest possible duration necessary to control symptoms (see GI and cardiovascular risks below).
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
Respiratory: Bronchospasm may be precipitated in patients suffering from, or with a previous history of, bronchial asthma or allergic disease.
Other NSAIDs: The use of Nurofen Cold & Flu with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.
SLE and mixed connective tissue disease: Systemic lupus erythematosus and mixed connective tissue disease – increased risk of aseptic meningitis.
Renal:  Moderate to severe renal impairment as renal function may further deteriorate, especially in dehydrated children and adolescents. Renal tubular acidosis and hypokalaemia may occur following acute overdose and in patients taking ibuprofen products over long periods at high doses (typically greater than 4 weeks), including doses exceeding the recommended daily dose.
Hepatic: Hepatic dysfunction.
Cerebrovascular effects: Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of occlusive vascular disease, hypertension and/or heart failure as fluid retention, hypertension and oedema have been reported in associated with NSAID therapy.
Clinical trial and epidemiological data suggest that the use of ibuprofen, particularly at high doses (2400mg daily) and in long-term treatment 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. ≤1200mg daily) is associated with an increased risk of myocardial infarction.
Impaired female fertility: There is limited evidence that drugs which inhibit cyclooxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible upon withdrawal of treatment.
Gastrointestinal: NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) as these conditions may be exacerbated.
GI 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.
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, and the elderly. These patients should commence treatment on the lowest dose available.
Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin.
When GI bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn.
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 systems or ischaemic colitis develop.
Severe cutaneous adverse reactions (SCARS): Severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP) which can be life-threatening or fatal, have been reported in association with the use of ibuprofen and pseudoepherine-containing products. This acute pustular eruption may occur within the first 2 days of treatment, with fever, and numerous, small, mostly non-follicular pustules arising on a widespread oedematous erythema and mainly localized on the skin folds, trunk, and upper extremities. Patients should be carefully monitored. If signs and symptoms such as pyrexia, erythema, or many small pustules are observed, most of these reactions occurred within the first month. If signs and symptoms suggestive of these reactions appear, this medicine should be withdrawn immediately.
Masking of symptoms of underlying infections: This medicinal product can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection. This has been observed in bacterial community acquired pneumonia and bacterial complications to varicella. When this medicine is administered for fever or pain relief in relation to infection, monitoring of infection is advised.
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.
Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS): Cases of PRES and RCVS have been reported with the use of pseudoephedrine containing products. The risk is increased in patients with severe or uncontrolled hypertension, or with severe acute or chronic kidney disease/renal failure. Pseudoephedrine should be discontinued and immediate medical assistance sought if the following symptoms occur: sudden severe headache or thunderclap headache, nausea, vomiting, confusion, seizures and/or visual disturbances. Most reported cases of PRES and RCVS resolved following discontinuation and appropriate treatment.
Kounis syndrome: Cases of Kounis syndrome have been reported in patients treated with this medicine. Kounis syndrome has been defined as cardiovascular symptoms secondary to an allergic or hypersensitive reaction associated with constriction of coronary arteries and potentially leading to myocardial infarction.
Other:
* To be used with caution in patients with cardiovascular disease, tachycardia, hypertension, angina pectoris, hyperthyroidism, diabetes, closed angle glaucoma or elevated intraocular pressure, prostatic enlargement, hyperexcitability.
* To be used with caution in combination with antihypertensives including adrenergic neurone blockers & Beta blockers. The effects of a single dose on the blood pressure of these patients should be observed before recommending repeated or unsupervised treatment.
* To be used with caution with other sympathomimetic agents such as decongestants, appetite suppressants and amphetamine-like psycho-stimulants.
* If hallucinations, restlessness, or sleep disturbances are experienced whilst taking the product, use of the product should be discontinued.

The most commonly observed adverse events are with ibuprofen are
gastrointestinal in nature.See prescribing information for full details.

Ibuprofen (like other NSAIDs) should be avoided in combination with:
Acetylsalicylic Acid (Aspirin): Unless low-dose Acetylsalicylic Acid (aspirin)
(not above 75mg daily) has been advised by a doctor, as this may increase the
risk of adverse reactions.
Experimental data suggest that ibuprofen may inhibit the effect of low dose
Acetylsalicylic Acid (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.
Other NSAIDs including cyclooxygenase-2 selective inhibitors: Avoid
concomitant use of two or more NSAIDs as this may increase the risk of adverse
effects.
Ibuprofen should be used with caution in combination with:
Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin.
Antihypertensives and diuretics: NSAIDS and pseudoephedrine may diminish
the effects of these drugs. Diuretics can increase the risk of nephrotoxicity of
NSAIDs.
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs):
increased risk of gastrointestinal bleeding.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and
increase plasma glycoside levels.
Sympathomimetics such as pseudoephedrine may increase risk of
dysrhythmias.
Lithium: There is evidence for potential increases in plasma levels of lithium.
Methotrexate: There is a potential for an increase in plasma methotrexate.
Ciclosporin: Increased risk of nephrotoxicity.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone
administration as NSAIDs can reduce the effects of mifepristone.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given
with tacrolimus.
Zidovudine: Increased risk of haematological toxicity when NSAIDs are given
with zidovudine. There is evidence of an increased risk of haemarthroses and
haematoma in HIV(+) haemophiliacs receiving concurrent treatment with
zidovudine and ibuprofen.
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.
Monoamine oxidase inhibitors (MAOIs) and/or Reversible inhibitors of
monoamine oxidase A (RIMAs): should not be given to patients receiving
MAOI therapy or within 14 days of stopping treatment: increased risk of
hypertensive crisis.
Ergot alkaloids (ergotamine & methysergide): increased risk of ergotism.
Other sympathomimetic agents such as decongestants, amphetamine-like
psychostimulants and appetite suppressants: pseudoephedrine may potentiate their effects. Risk of hypertension.
Oxytocin: risk of hypertension.
Anticholinergics: the effect of pseudoephedrine may be diminished/enhanced
by tricyclic antidepressants.
Guanethidine, reserpine and methyldopa: the effect of pseudoephedrine
may be diminished.
Moclobemide: risk of hypertensive crisis

Pregnancy: Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. From the 20th week of pregnancy onward, Nurofen 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 during the first and second trimester of pregnancy, Nurofen should not be given unless clearly necessary. If Nurofen 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. Antenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to Nurofen for several days from gestational week 20 onward. Nurofen should be discontinued if oligohydramnios or ductus arteriosus constriction are found.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to: cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction (see above); which may progress to renal failure with oligohydroamniosis; the mother and the neonate, at the end of the pregnancy, to: possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses; inhibition of uterine contractions resulting in delayed or prolonged labour. Consequently, Nurofen is contraindicated during the third trimester of pregnancy.
Lactation: Although ibuprofen appears in breast milk in very low concentrations, significant amounts of Pseudoephedrine are secreted into breast milk and the use of Nurofen Cold and Flu during lactation should be avoided.

In children ingestion of more than 400 mg/kg ibuprofen may cause symptoms. In adults the dose response effect 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.
As with other sympathomimetics, Pseudoephedrine overdose may cause symptoms of central nervous system and cardiovascular stimulation,
including: Irritability, restlessness, tremor, palpitations, convulsions, urinary retention, hypertension, tachycardia and cardiac arrhythmias.
Difficulty in micturition, nausea, vomiting may also occur in Pseudoephedrine
overdose.
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. Prolonged use at higher than recommended doses may result in severe hypokalaemia and renal tubular acidosis. Symptoms may include reduced level of consciousness and generalised weakness
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.
A rapidly-acting alpha blocker, such as phentolamine, may be given to reverse alpha1-mediated effects such as hypertension, while a beta blocker may be given for beta1-mediated effects such as cardiac arrhythmias. In severe
hypertension, rapidly-acting vasodilators such as glyceryl trinitrate have also been used.

Shelf life: 3 years.
Storage: Store below 25°C.