1 Name of Medicine
Ibuprofen and paracetamol.
2 Qualitative and Quantitative Composition
Nuromol Dual Action Pain Relief contains ibuprofen 200 mg and paracetamol 500 mg as active ingredients. This formulation may contain traces of sulfites, as this formulation contains gelatin. For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Nuromol Dual Action Pain Relief is a white coloured, oblong shaped and opaque soft gelatin capsules containing white coloured oily mass.
4.1 Therapeutic Indications
Nuromol Dual Action Pain Relief is indicated for temporary relief of acute (short term) pain and/or inflammation associated with headache, migraine headache, tension headache, sinus pain, toothache, dental procedures, backache, muscular aches and pains, period pain, sore throat, tennis elbow, rheumatic pain and arthritis, and the aches and pains associated with colds and flu.
4.2 Dose and Method of Administration
The lowest effective dose should be used for the shortest duration necessary to relieve symptoms (see Section 4.4).
Adults under 65 years of age.
1 soft capsule, 3 times a day (every 8 hours) when necessary. Not to be taken for more than 3 days at a time unless advised by a doctor.
Children from 12 years of age and adolescents.
1 soft capsule, 3 times a day (every 8 hours) when necessary. Not to be taken for more than 2 days at a time unless advised by a doctor.
Elderly.
Nuromol Dual Action Pain Relief is contraindicated in adults aged 65 years and over.
Pregnancy.
See Section 4.3 Contraindications; Section 4.6 Fertility, Pregnancy and Lactation.4.3 Contraindications
This product is contraindicated:
In patients with a known hypersensitivity to ibuprofen, paracetamol or any other constituent of the medicinal product.
In patients with a history of hypersensitivity reactions (e.g. bronchospasm, angioedema, rhinitis or urticaria) associated with aspirin or other anti-inflammatory drugs or analgesic drugs.
In patients with a history of, or an existing gastrointestinal ulceration/perforation or bleed, or other stomach disorder.
In patients with impaired hepatic function, impaired renal function or heart failure.
In patients with asthma.
In pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation).
In patients with conditions that predispose to renal failure.
In concomitant use with ibuprofen or other NSAID-containing products, including cyclooxygenase-2 (COX-2) specific inhibitors and aspirin or other anti-inflammatories as there is an increased risk of adverse reactions.
In concomitant use with other paracetamol-containing products as there is an increased risk of serious adverse effects; patients should be advised not take with any other paracetamol containing products. Immediate medical advice should be sought if this occurs, even if they feel well, as this can result in an overdose.
In patients aged 65 years and over and in children under 12 years.
In patients undergoing treatment of perioperative pain in setting of coronary artery bypass surgery (CABG).
See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions for additional information.
4.4 Special Warnings and Precautions for Use
The hazard of paracetamol overdose is greater in patients with non-cirrhotic alcoholic liver disease. Immediate medical advice should be sought in the event of an overdose, even if the patient feels well, because of the risk of delayed, serious liver damage.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
Diabetes.
Caution is required in patients suffering from diabetes. Paracetamol falsely elevates continuous blood glucose monitor (CGM) readings compared to finger stick (BG meter) readings. This is applicable for those using CGM devices with or without an automated insulin delivery pump e.g. in type I diabetes.
Respiratory disorders.
Caution is required in patients with a history of bronchial asthma or allergic disease since NSAIDs have been reported to precipitate bronchospasm. The product is contraindicated in asthma (see Section 4.3 Contraindications).
Renal and hepatic impairment.
The administration of NSAIDs may cause a dose-dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. The product is contraindicated in patients with impaired renal or liver function or heart failure and in patients 65 years of age or older (see Section 4.3 Contraindications). Renal function should be monitored in other at risk patients.
As with other NSAIDs elevations of one or more liver function tests may occur in up to 15% of patients. These abnormalities may progress, may remain essentially unchanged or may resolve with continued therapy. Meaningful elevations (three times the upper limit of normal) of ALT or AST occurred in controlled clinical trials in less than 1% of patients.
Patients should be advised to remain alert for hepatotoxicity and be informed about the signs and/or symptoms of hepatotoxicity (e.g. nausea, fatigue, lethargy, pruritus, jaundice, abdominal tenderness in the right upper quadrant and "flu-like" symptoms).
Cardiovascular and cerebrovascular effects.
Observational studies have indicated that NSAIDs may be associated with an increased risk of serious cardiovascular events, including myocardial infarction and stroke, which may increase with dose or duration of use.
Patients with cardiovascular disease, history of atherosclerotic cardiovascular disease or cardiovascular risk factors may also be at greater risk.
Patients should be advised to remain alert for such cardiovascular events, even in the absence of previous cardiovascular symptoms. Patients should be informed about signs and/or symptoms of serious cardiovascular toxicity and the steps to take if they occur.
Fluid retention, hypertension and oedema have been reported in association with NSAID therapy. Patients taking antihypertensives with NSAIDs may have an impaired antihypertensive response. Appropriate monitoring and advice are required for patients with a history of hypertension. The product is contraindicated in patients with heart failure (see Section 4.3 Contraindications).
Clinical trial data suggest that the use of ibuprofen, particularly at high doses (2400 mg daily) may be associated with an increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g. < 1200 mg daily) is associated with an increased risk of myocardial infarction.
Patients with uncontrolled hypertension, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with Nuromol Dual Action Pain Relief after careful consideration. Similar consideration should be made before initiating treatment for patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus and smoking). The product is contraindicated in heart failure (see Section 4.3 Contraindications).
Cases of Kounis syndrome have been reported in patients treated with ibuprofen containing products such as Nuromol Dual Action Pain Relief liquid capsules. 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.
Gastrointestinal bleeding, ulceration and perforation.
Gastrointestinal (Gl) bleeding, ulceration and 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 Gl events.
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 (SSRIs), or antiplatelet agents.
The product is contraindicated in patients with a history of GI toxicity including ulceration (see Section 4.3 Contraindications).
When Gl bleeding or ulceration occurs in patients receiving ibuprofen and paracetamol, the treatment should be withdrawn.
SLE and mixed connective tissue disease.
In patient with systemic lupus erythematosus (SLE) and mixed connective tissue disease disorders there may be an increased risk of aseptic meningitis.
Skin and subcutaneous tissue disorders.
Dermatological effects.
Severe cutaneous adverse reactions (SCAR), exfoliative dermatitis, Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia with systemic symptoms (see Drug reaction with eosinophilia with systemic symptoms (DRESS)), toxic epidermal necrolysis (TEN), and acute generalised exanthematous pustulosis (AGEP), which can be life threatening or fatal, have been reported in association with the use of ibuprofen and paracetamol. Most of these reactions occurred within the first month. If signs and symptoms suggestive of these reactions appear, Nuromol Dual Action Pain Relief liquid capsules should be withdrawn immediately, and an alternative treatment considered (as appropriate).
Severe skin reactions such as acute generalised exanthematous pustulosis (AGEP) has been reported in relation to ibuprofen-containing products. The acute pustular eruption may occur with ibuprofen-containing products. The 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 localised 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, administration of Nuromol Dual Action Pain Relief liquid capsules should be discontinued, and appropriate measures taken if needed.
Drug reaction with eosinophilia with systemic symptoms (DRESS).
DRESS has been reported in patients using NSAIDs. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, haematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present.
Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue the NSAID and evaluate the patient immediately.
Masking of symptoms of underlying infections.
Nuromol Dual Action Pain Relief liquid capsules 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 Nuromol Dual Action Pain Relief liquid capsules is administered for fever or pain relief in relation to infection, monitoring the infection is advised. In non-hospital settings, the patient should consult a doctor if symptoms persist or worsen.
Paediatric use.
Nuromol Dual Action Pain Relief is contraindicated in children under 12 years of age since no investigations have been carried out with this product in this age group.
Use in the elderly.
Nuromol Dual Action Pain Relief is contraindicated in adults aged 65 years and over.
Effects on laboratory tests.
No information is available regarding Nuromol Dual Action Pain Relief and laboratory tests.
See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions for additional information.4.5 Interactions with Other Medicines and Other Forms of Interactions
This product is contraindicated in combination with:
Aspirin (acetylsalicylic acid).
Unless low-dose acetylsalicylic acid (not above 75 mg daily) has been advised by a doctor, as this may increase the risk of adverse reactions (see Section 4.4). Experimental data suggests that ibuprofen may inhibit the effect of low dose acetylsalicylic acid 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 (see Section 5.1).
Other paracetamol containing products.
Other NSAIDs including cyclooxygenase-2 selective inhibitors.
Other anti-inflammatories and analgesics.
The concomitant use may increase the risk of adverse reactions.
This product (like any other paracetamol containing products) should be used with caution in combination with:
Chloramphenicol.
Increased plasma concentration of chloramphenicol.
Cholestyramine.
The speed of absorption of paracetamol is reduced by cholestyramine. Therefore, cholestyramine should not be taken within one hour if maximal analgesia is required.
Flucloxacillin.
Concurrent use of paracetamol and flucloxacillin is associated with an increased risk of metabolic acidosis especially in patients with severe renal impairment, sepsis, malnutrition and chronic alcoholism.
Isoniazid.
The toxicity of paracetamol may be increased by isoniazid.
Liver enzyme-inducing drugs.
Drugs which induce or regulate liver microsomal enzymes (cytochrome P450 isoenzyme 2E1), such as anticonvulsants (including phenytoin, barbiturates, carbamazepine) and alcohol, may increase the hepatoxic potential of paracetamol.
Metoclopramide and domperidone.
The absorption of paracetamol is increased by metoclopramide and domperidone. However, concurrent use need not be avoided.
Warfarin.
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.
This product (like any other ibuprofen containing products and NSAIDs) should be used with caution in combination with:
Anticoagulants.
NSAIDs may enhance the effects of anticoagulants, i.e. warfarin.
Antihypertensives.
NSAIDs may reduce the effects of these drugs.
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs).
Increased risk of gastrointestinal bleeding.
Cardiac glycosides.
NSAIDs may exacerbate cardiac failure, reduce glomerular filtration rate (GFR) and increase plasma glycoside levels.
Ciclosporin.
Increased risk of nephrotoxicity.
Corticosteroids.
Increased risk of gastrointestinal ulceration or bleeding.
Diuretics.
Reduced diuretic effect. Diuretics may increase the risk of nephrotoxicity of NSAIDs.
Lithium.
Decreased elimination of lithium.
Methotrexate.
Decreased elimination of methotrexate.
Mifepristone.
NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
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.
Tacrolimus.
Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Zidovudine.
Increased risk of haematological toxicity when NSAIDs are given concomitantly with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV+ haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.4.6 Fertility, Pregnancy and Lactation
Effects on fertility.
The use of the product may impair female fertility and is not recommended in women attempting to conceive.
(Category C)
Drugs which owing to their pharmacological effects have caused or may be suspected of causing harmful effects on the human foetus or neonate without causing malformation. These effects may be reversible.
There is no experience of use of this product in humans during pregnancy. Therefore, this product is contraindicated for use during pregnancy.
Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. Use of NSAIDs during the last trimester of pregnancy may cause effects on the foetal cardiovascular system (risk of closure of ductus arteriosus), and the onset of labour may be delayed, and the duration increased with an increased bleeding tendency in both mother and child.
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol use at the recommended dosage.
There is inadequate information regarding the use of Nuromol Dual Action Pain Relief in pregnancy. Therefore, this medicine should not be used during pregnancy or in patients planning to become pregnant.
Oligohydramnios and neonatal renal impairment.
Use of NSAIDs from about 20 weeks gestation may cause neonatal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.
These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation.
Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some post-marketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If, after careful consideration of alternative treatment options for pain management, NSAID treatment is necessary from about 20 weeks, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if treatment extends beyond 48 hours. Discontinue treatment with NSAIDs if oligohydramnios occurs.
Ibuprofen and its metabolites can pass in very small amounts (0.0008% of the maternal dose) into the breast milk. No harmful effects to infants are known.
Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breastfeeding.
Therefore, it is not necessary to interrupt breastfeeding for short term treatment with the recommended dose of this product.4.7 Effects on Ability to Drive and Use Machines
Patients experiencing dizziness or drowsiness while taking Nuromol Dual Action Pain Relief should refrain from driving a vehicle or operating machines.
4.8 Adverse Effects (Undesirable Effects)
Clinical trials with this product have not indicated any other undesirable effects other than those for ibuprofen or paracetamol alone.
In clinical trials, the product administered in single or multiple doses was shown to have a safety profile comparable to that of placebo. The percentage of subjects who experienced side effects, as well as the individual side effects seen, were similar to the well documented profiles of paracetamol and ibuprofen administered alone.
The following is a list of adverse effects from pharmacovigilance data experienced by patients taking ibuprofen alone or paracetamol alone in short term and long term use.
Adverse events may be minimized by using the minimum effective dose for the shortest duration necessary to control symptoms.
Common (occur in > 1% and < 10%).
Gastrointestinal.
Abdominal pain, diarrhoea, dyspepsia, nausea, stomach discomfort and vomiting.
Investigations.
Alanine aminotransferase increased, gamma glutamyl transferase increased and liver function tests abnormal with paracetamol. Blood creatinine increased and blood urea increased.
Skin and subcutaneous tissue disorders.
Hyperhidrosis.
Uncommon (occur in > 0.1% and < 1%).
Gastrointestinal.
Flatulence and constipation, peptic ulcer, perforation or gastrointestinal haemorrhage, with symptoms of melaena, haematemesis sometimes fatal, particularly in the elderly. Ulcerative stomatitis and exacerbation of ulcerative colitis and Crohn's disease. Less frequently gastritis has been observed and pancreatitis reported.
Skin and subcutaneous tissue disorders.
Rashes of various types (including urticarial) and pruritus. Angioedema and swelling face. Acute generalised exanthematous pustulosis (AGEP).
Investigations.
Aspartate aminotransferase increased, blood alkaline phosphatase increased, blood creatine phosphokinase increased, blood creatinine increased, haemoglobin decreased and platelet count increased.
Nervous system disorders.
Headache and dizziness.
Immune system disorders.
Hypersensitivity with urticaria and pruritus.
Very rare (occur in < 0.01%).
Blood and lymphatic system disorders.
Haematopoietic disorders (agranulocytosis, anaemia, aplastic anaemia, haemolytic anaemia, leucopaenia, neutropaenia, thrombocytopaenia and pancytopaenia). First signs are fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising and nose bleeds.
Immune system disorders.
Hypersensitivity reactions have been reported. These may consist of non-specific allergic reactions and anaphylaxis. Symptoms of severe hypersensitivity reactions can include facial, tongue and larynx swelling, dyspnoea, tachycardia, hypotension, anaphylaxis, angioedema or severe shock.
Psychiatric disorders.
Confusion, depression and hallucinations.
Nervous system disorders.
Paraesthesia, optic neuritis and somnolence. Single cases of aseptic meningitis in patients with existing autoimmune disorders (e.g. systemic lupus erythematosus and mixed connective tissue disease) during treatment with ibuprofen, with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation have been observed.
Eye disorders.
Visual disturbance.
Ear and labyrinth disorders.
Tinnitus and vertigo.
Cardiac disorders.
Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment. Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high doses (2400 mg daily), and in long term treatment may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).
Respiratory, thoracic and mediastinal disorders.
Respiratory reactivity including asthma, exacerbation of asthma, bronchospasm and dyspnoea.
Hepatobiliary disorders.
Abnormal liver function, hepatitis and jaundice. In overdose, paracetamol can cause acute hepatic failure, hepatic failure, hepatic necrosis and liver injury.
Skin and subcutaneous tissue disorders.
Purpura and photosensitivity. Exfoliative dermatoses. Severe cutaneous adverse reactions (SCARs), bullous reactions including bullous erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Renal and urinary disorders.
Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, and acute and chronic renal failure.
General disorders and administration site conditions.
Fatigue and malaise.
Unknown frequency (cannot be estimated from the available data).
Pregnancy, puerperium, and perinatal conditions.
Oligohydramnios, neonatal renal impairment.
Skin and subcutaneous tissue disorders.
Drug reaction with eosinophilia with systemic symptoms (DRESS).
Cardiac disorders.
Kounis syndrome.
Hypersensitivity reactions have been reported following treatment with both paracetamol and ibuprofen. These may consist of:
Non-specific allergic reactions and anaphylaxis.
Respiratory tract reactivity e.g. asthma, aggravated asthma, bronchospasm and dyspnoea.
Assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema and more rarely bullous dermatoses (including toxic epidermal necrolysis and bullous erythema multiforme).
Reporting suspected adverse effects.
Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.4.9 Overdose
In case of overdose, immediately contact the Poisons Information Centre in Australia on 13 11 26 and in New Zealand call 0800 764 766 for advice.
Paracetamol.
Liver damage is possible in adults who have taken 10 g (equivalent to 20 tablets) or more of paracetamol. Ingestion of 5 g (equivalent to 10 tablets) or more of paracetamol may lead to liver damage if the patient has one or more of the risk factors below:
a) Is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes.
b) Regularly consumes alcohol in excess of recommended amounts.
c) Is likely to be glutathione depleted e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
Symptoms.
Symptoms of paracetamol overdose in the first 24 hours include pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion as liver function tests become abnormal. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. CNS stimulation and delirium may occur initially, followed by CNS depression, stupor, hypothermia, rapid shallow breathing, hypotension and circulatory failure. Shock may also develop, as well as seizures and coma. Cardiac arrhythmias and pancreatitis have been reported.
Additional information on special patient populations.
An increased risk of liver damage from paracetamol overdosing has been associated with: patients taking isoniazid.
Management.
Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines.
Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable).
Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol, however the maximum protective effect is obtained up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply after this time.
If required, the patient should be given intravenous N-acetylcysteine in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital.
Patients who present with serious hepatic dysfunction beyond 24 hours from ingestion should be managed in accordance with established guidelines.
Ibuprofen.
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 prolong the prothrombin time (PT) and increase the international normalised ratio (INR), probably due to interference with the actions of circulating clotting factors. Acute renal failure and liver damage may occur if there is co-incident dehydration. Exacerbation of asthma is possible in asthmatics.
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.5 Pharmacological Properties
5.1 Pharmacodynamic Properties
The pharmacological actions of ibuprofen and paracetamol differ in their site and mode of action. These complementary modes of action result in greater antinociception than the single actives alone.
Ibuprofen possesses analgesic, antipyretic and anti-inflammatory properties, similar to other nonsteroidal anti-inflammatory drugs (NSAIDs). Its mechanism of action is unknown, but it is thought to be through peripheral inhibition of cyclooxygenases and subsequent prostaglandin synthetase inhibition.
Paracetamol is a para-aminophenol derivative that exhibits analgesic and antipyretic activity. Paracetamol has minimal anti-inflammatory action. The precise mechanism of action remains uncertain; it is believed to include inhibition of prostaglandin synthesis, primarily within the central nervous system.
5.2 Pharmacokinetic Properties
Absorption.
Ibuprofen is well absorbed from the gastrointestinal tract and is extensively bound to plasma proteins. Ibuprofen diffuses into the synovial fluid. Plasma levels of ibuprofen from this product are detected from 5 minutes with peak plasma concentrations achieved within 1-2 hours after ingestion on an empty stomach. When taken with food, peak plasma levels are delayed by a median of 25 minutes, but the overall extent of absorption is equivalent.
Paracetamol is readily absorbed from the gastrointestinal tract. Plasma protein binding is negligible at usual therapeutic concentrations, although this is dose-dependent. Plasma levels of paracetamol from this product are detected from 5 minutes with peak plasma concentrations occurring at 0.5-0.67 hours after ingestion on an empty stomach.
Metabolism.
Ibuprofen is metabolised in the liver to two major metabolites with primary excretion via the kidneys, either as such or as major conjugates, together with a negligible amount of unchanged ibuprofen.
Paracetamol is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates, with about 10% as glutathione conjugates. A minor hydroxylated metabolite, which is usually produced in very small amounts by mixed function oxidases in the liver and detoxified by conjugation with liver glutathione, may accumulate following paracetamol overdose and cause liver damage.
Excretion.
Excretion of ibuprofen by the kidney is both rapid and complete. The elimination half-life is approximately 2 hours.
Less than 5% of paracetamol is excreted as unchanged paracetamol. The elimination half-life is approximately 3 hours.
No significant differences in the paracetamol or ibuprofen pharmacokinetic profiles are observed in the elderly.
The bioavailability and pharmacokinetic profiles of ibuprofen and paracetamol taken individually are not altered when taken in combination as a single or repeat dose.
5.3 Preclinical Safety Data
Genotoxicity.
No information is available regarding Nuromol Dual Action Pain Relief and genotoxicity.
Carcinogenicity.
No information is available regarding Nuromol Dual Action Pain Relief and carcinogenicity.6 Pharmaceutical Particulars
6.1 List of Excipients
Following are the list of excipients present in the formulation of Nuromol Dual Action Pain Relief soft capsules: povidone, propylene glycol, macrogol 400, macrogol 4000, gelatin, partially dehydrated liquid sorbitol, fumaric acid, titanium dioxide, purified water.
6.2 Incompatibilities
Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
6.3 Shelf Life
In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.
6.4 Special Precautions for Storage
Store below 30°C, protect from light and moisture.
6.5 Nature and Contents of Container
Nuromol Dual Action Pain Relief are packed in Alu-PVC/PVDC white opaque film blister in packs of 6s, 10s, 12s, 20s and 24s.
6.6 Special Precautions for Disposal
In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.
6.7 Physicochemical Properties
Chemical structure.
Ibuprofen.
Paracetamol.
CAS numbers.
15687-27-1 (for ibuprofen) and 103-90-2 (for paracetamol).7 Medicine Schedule (Poisons Standard)
S2 for pack size 10 soft capsules.
S3 for pack size 20 soft capsules.
Summary Table of Changes
