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  • Combodex IV
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    Active Ingredient *
    Paracetamol 10 mg/ml
    Ibuprofen (as sodium dihydrate) 3 mg/ml

    Status in Israel

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft


    10 X 100 ml

    not in the basket chart


    Administer one vial (100 mL) as a 15-minute infusion every 6 hours, as necessary. Do not exceed a total daily dose of 4000 mg (4 g) paracetamol.
    Special populations:
    Paediatric population:
    The safety and efficacy in children aged under 18 years have not been established.
    Elderly: Clinical studies did not include sufficient numbers of subjects 65 years of age and over to determine whether they respond differently to younger subjects. Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients are at increased risk for serious GI adverse events.
    Renal impairment: Caution is also recommended in patients with pre-existing renal disease. No information is available from controlled clinical studies regarding the use in patients with advanced renal disease. If therapy must be initiated in patients with advanced renal disease, closely monitor the patient’s renal function.
    Hepatic impairment:
    The use of paracetamol at higher than recommended doses can lead to hepatotoxicity and even hepatic failure and death.
    A patient with symptoms and/or signs suggesting liver dysfunction, or with abnormal liver test values, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with ibuprofen. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash, etc.), this medicinal product should be discontinued.
    Adverse gastrointestinal events: To minimise the potential risk for an adverse GI event in patients treated with a NSAID, use the lowest effective dose for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulcerations and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI event is suspected.
    This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered.
    See prescribing information for full details.


    Indicated in adults for the relief of mild to moderate pain and the reduction of fever, where an intravenous route of administration is considered clinically necessary.


    • known hypersensitivity to paracetamol, ibuprofen, other NSAIDs or to any of   the excipients;
    • severe heart failure (NYHA Class IV);
    • active alcoholism, as chronic excessive alcohol ingestion may predispose   patients to hepatotoxicity (due to the paracetamol component);
    • Patients who have experienced asthma, urticaria, or allergic-type reactions after taking acetylsalicylic acid or other NSAIDs;
    • history of gastrointestinal bleeding or perforation related to previous NSAID  therapy;
    • active, or a history of, recurrent peptic ulceration/haemorrhage (two or more        distinct episodes of proven ulceration or bleeding);
    • severe hepatic failure or severe renal failure;
    • cerebrovascular or other active bleeding;
    • blood clotting disorders and conditions involving an increased tendency to  bleed;
    • severe dehydration (caused by vomiting, diarrhoea or insufficient fluid intake);
    • during the third trimester of pregnancy;
    See prescribing information for full details.

    Special Precautions

    Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms. Use of the recommended maximum dose of 100 mL every 6 hours has only been studied for a period of up to 2 days.
    The use of this medicinal product with concomitant NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided.
    In order to avoid the risk of overdose,
    • check that other medicinal products do not contain paracetamol,
    • observe the maximum recommended doses.
    Cardiovascular thrombotic events
    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, and smoking), particularly if high doses of ibuprofen (2400 mg/day) are required.
    Hepatic impairment
    The use of paracetamol at higher than recommended doses can lead to hepatotoxicity and even hepatic failure and death. Also, patients with impaired liver function or a history of liver disease, and who are on long term ibuprofen therapy or paracetamol treatment, should have hepatic function monitored at regular intervals, as ibuprofen has been reported to have a minor and transient effect on liver enzymes. Dose reduction is recommended in patients showing signs of worsening hepatic function. Treatment should be stopped in those patients who develop severe liver failure.
    Severe hepatic reactions, including jaundice and cases of fatal hepatitis, though rare, have been reported with ibuprofen as with other NSAIDs. If abnormal liver tests persist or worsen, or if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash, etc.), ibuprofen should be discontinued. Both active drugs have been reported to cause hepatotoxicity and even hepatic failure, especially paracetamol.
    Renal impairment
    Paracetamol can be used in patients with chronic renal disease without dosage adjustment. There is minimal risk of paracetamol toxicity in patients with moderate to severe renal failure. However, for the ibuprofen component of this product, caution should be used when initiating treatment with ibuprofen in patients with dehydration. The two major metabolites of ibuprofen are excreted mainly in the urine and impairment of renal function may result in their accumulation. The significance of this is unknown. NSAIDs have been reported to cause nephrotoxicity in various forms: interstitial nephritis, nephritic syndrome and renal failure. Renal impairment from ibuprofen use is usually reversible. In patients with renal, cardiac or hepatic impairment, those taking diuretics and ACE inhibitors, and the elderly, caution is required since the use of NSAIDs may result in deterioration of renal function. The dose should be kept as low as possible and renal function should be monitored in these patients. Treatment should be stopped in those patients who develop severe renal failure.
    Combination use of ACE inhibitors or angiotensin receptor antagonists, anti-inflammatory drugs and thiazide diuretics
    The use of an ACE inhibiting drug (ACE-inhibitor or angiotensin receptor antagonist), an anti- inflammatory drug (NSAID or COX-2 inhibitor) and thiazide diuretic at the same time increases the risk of renal impairment. This includes use in fixed-combination products containing more than one class of drug. Combined use of these medications should be accompanied by increased monitoring of serum creatinine, particularly at the institution of the combination. The combination of drugs from these three classes should be used with caution particularly in elderly patients or those with pre-existing renal impairment.
    No reduction in recommended dosage is necessary. However, caution should be taken with regard to the use of ibuprofen as it should not be taken by adults over the age of 65 without consideration of co- morbidities and co-medications because of an increased risk of adverse effects, in particular heart failure, gastrointestinal ulceration and renal impairment.
    Haematological effects
    Blood dyscrasias have been rarely reported. Patients on long-term therapy with ibuprofen should have regular haematological monitoring.
    Anaphylactoid reactions
    As standard practice during intravenous infusion, close patient monitoring is recommended, especially at the beginning of the infusion to detect any anaphylactic reaction caused by the active substance or the excipients.
    Severe acute hypersensitivity reactions (e.g. anaphylactic shock) are very rarely observed. At the first signs of a hypersensitivity reaction following the administration of this drug, therapy must be stopped and symptomatic treatment must be established. Medically required measures, in line with the symptoms, must be initiated by specialist personnel.
    Coagulation defects
    Like other NSAIDs, ibuprofen can inhibit platelet aggregation. Ibuprofen has been shown to prolong bleeding time (but within the normal range), in normal subjects. Because this prolonged bleeding effect may be exaggerated in patients with underlying haemostatic defects, products containing ibuprofen should be used with caution in persons with intrinsic coagulation defects and those on anti-coagulation therapy. Patients with coagulation disorders or those undergoing surgery should be monitored. Special medical vigilance is required for use in patients immediately after undergoing major surgery.
    Gastrointestinal events
    Gastrointestinal (GI) bleeding, ulceration or perforation, which can be fatal, have 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 in the elderly. 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 requiring concomitant low dose acetylsalicylic acid, or other medicinal products likely to increase gastrointestinal risk. 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 acetylsalicylic acid.
    Due to the ibuprofen component, this medicinal product should be given with care to patients with a history of GI disease (ulcerative colitis, Crohn’s disease) as well as in patients with porphyria.
    The elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation which may be fatal.
    This product should be discontinued if there is any evidence of gastrointestinal bleeding or ulceration.
    NSAIDs may lead to onset of new hypertension or worsening of pre-existing hypertension and patients taking antihypertensive medicines with NSAIDs may have an impaired anti-hypertensive response. Caution is advised when prescribing NSAIDs to patients with hypertension. Blood pressure should be monitored closely during initiation of NSAID treatment and at regular intervals thereafter.
    Heart failure
    Fluid retention and oedema have been observed in some patients taking NSAIDs, therefore caution is advised in patients with fluid retention or heart failure.
    Severe skin reactions
    NSAIDs may very rarely cause serious cutaneous adverse events such as exfoliative dermatitis, toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), which can be fatal and occur without warning. Acute generalised exanthematous pustulosis (AGEP) has been reported in relation to ibuprofen-containing products. Patients appear to be at highest risk for 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.
    Patients should be advised of the signs and symptoms of serious skin reactions and to consult their doctor at the first appearance of a skin rash or any other sign of hypersensitivity.
    Exceptionally, varicella can cause serious cutaneous and soft tissues infectious complications. To date, the contributing role of NSAIDs in the worsening of these infections cannot be ruled out. Thus, it is advisable to avoid use in case of varicella.
    Pre-existing asthma
    Products containing ibuprofen should not be administered to patients with acetylsalicylic acid-sensitive asthma and should be used with caution in patients with pre-existing asthma.
    Ophthalmological effects
    Adverse ophthalmological effects have been observed with NSAIDs; accordingly, patients who develop visual disturbances during treatment with products containing ibuprofen should have an ophthalmological examination.
    Aseptic meningitis
    For products containing ibuprofen, aseptic meningitis has been reported only rarely, usually but not always in patients with systemic lupus erythematosus (SLE) or other connective tissue disorders.
    Potential laboratory test interferences
    Using current analytical systems, paracetamol does not cause interference with laboratory assays. However, there are certain methods with which the possibility of laboratory interference exists, as described below.
    Urine tests: Paracetamol in therapeutic doses may interfere with the determination of 5-hydroxyindoleacetic acid (5HIAA), causing false-positive results. False determinations may be eliminated by avoiding paracetamol ingestion several hours before and during the collection of the urine specimen.
    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 drug 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.
    Prolonged use of analgesics
    On prolonged use of analgesics, headache may occur which must not be treated by increasing the dose of the medicinal product.
    Caution is advised if paracetamol is administered concomitantly with flucloxacillin due to increased risk of high anion gap metabolic acidosis (HAGMA), particularly in patients with severe renal impairment, sepsis, malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism), as well as those using maximum daily doses of paracetamol. Close monitoring, including measurement of urinary 5-oxoproline, is recommended.
    Special precautions
    There is some evidence that drugs which inhibit cyclo-oxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on stopping the medicine.
    Ibuprofen should be used only after strict assessment of the benefit/risk in patients with congenital disorder of porphyrin metabolism (e.g. acute intermittent porphyria).
    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.
    Caution is required in patients with certain conditions, which may be made worse:
    • In patients who react allergically to other substances, as an increased risk of hypersensitivity reactions occurring also exists for them on use of this medicinal product.
    • In patients who suffer from hay fever, nasal polyps or chronic obstructive respiratory disorders as an increased risk exists for them of allergic reaction occurring. These may present as asthma attacks (so-called analgesic asthma), Quincke’s oedema or urticaria.
    This medicinal product contains 35.06 mg sodium per 100 mL vial, equivalent to 1.75% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
    See prescribing information for full details.

    Side Effects

    The most common side effects are: Dizziness, headache nervousness; Tinnitus (for medicines containing ibuprofen); Oedema, fluid retention (fluid retention generally responds promptly to discontinuation of the drug); Abdominal pain, diarrhoea, dyspepsia, nausea, stomach discomfort and vomiting, flatulence, constipation, slight gastrointestinal blood loss that may cause anaemia in exceptional cases; Rash (including maculopapular type), pruritus; Alanine aminotransferase increased, gamma- glutamyltransferase increased and liver function tests abnormal with paracetamol; Blood creatinine increased and blood urea increased.
    See prescribing information for full details.

    Drug interactions

    This medicinal product should not be taken with other medicinal products containing paracetamol, ibuprofen, acetylsalicylic acid, salicylates or with any other anti-inflammatory drugs (NSAIDs) unless under a doctor’s instruction.
    As with other ibuprofen-containing products, the following combinations with this drug should be avoided:
    • The dicumarol group: NSAIDs may increase the effect of anticoagulants such as warfarin. Experimental studies show that ibuprofen reinforces the effects of warfarin on bleeding time. NSAIDs and the dicumarol group are metabolised by the same enzyme, CYP2C9.
    • Antiplatelet agents: NSAIDs should not be combined with antiplatelet agents such as ticlopidine due to the additive inhibition of the platelet function (see below).
    • Methotrexate: NSAIDs inhibit the tubular secretion of methotrexate and some metabolic interaction with reduced clearance of methotrexate may also occur as a result. The risk of a potential interaction between an NSAID and methotrexate should also be taken into account in connection with low-dose treatment with methotrexate, especially in patients with renal impairment. Whenever combination treatment is given, renal function should be monitored.
    Caution should be exercised if both an NSAID and methotrexate are given within 24 hours, as the plasma levels of methotrexate can increase, resulting in increased toxicity. Accordingly, in high-dose treatment with methotrexate one should always avoid prescribing NSAIDs.
    • Acetylsalicylic acid: 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.
    • Lithium: Ibuprofen reduces the renal clearance of lithium, as a result of which serum lithium levels may rise. The combination should be avoided unless frequent checks of serum lithium can be carried out and a possible reduction in the dose of lithium made.
    • Cardiac glycosides: NSAIDs can exacerbate heart failure, reduce glomerular filtration and increase plasma cardiac glycoside (e.g. digoxin) levels.
    • Mifepristone: A decrease of the efficacy of the medicinal product can theoretically occur due to the antiprostaglandin properties of non-steroidal anti-inflammatory drugs (NSAIDs) including acetylsalicylic acid. Limited evidence suggests that co-administration of NSAIDs on the day of prostaglandin administration does not adversely influence the effects of mifepristone or the prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medical termination of pregnancy
    • ACE inhibitors and angiotensin-II antagonists: There is an increased risk of acute renal failure, usually reversible, in patients with renal impairment (e.g. dehydrated and/or elderly patients) when treatment with ACE inhibitors or angiotensin-II antagonists is given at the same time as NSAIDs, including selective cyclooxygenase-2 inhibitors. The combination should, therefore, be given with care to patients with renal impairment, especially elderly patients. Patients should be adequately hydrated and a check of renal function should be considered after the initiation of combination treatment and at regular intervals during treatment.
    • Beta-blockers: NSAIDs counteract the antihypertensive effect of beta-adrenoceptor blocking drugs.
    • Sulphonylureas: There are rare reports of hypoglycaemia in patients on sulphonylurea medications receiving ibuprofen.
    • 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 increased risk of developing convulsions.
    • Thiazides, thiazide-related preparations and loop diuretics: NSAIDs can counteract the diuretic effect of furosemide and bumetanide, possibly through inhibition of prostaglandin synthesis. They can also counteract the antihypertensive effect of thiazides.
    • Potassium sparing diuretics: The concomitant use may lead to hyperkalaemia.
    • Aminoglycosides: NSAIDs may reduce the excretion of aminoglycosides.
    • Selective serotonin re-uptake inhibitors (SSRIs): SSRIs and NSAIDs each entail an increased risk of bleeding, e.g. from the gastrointestinal tract. This risk is increased by combination therapy. The mechanism may possibly be linked to reduced uptake of serotonin in the platelets.
    • Cyclosporine: The concomitant administration of NSAIDs and cyclosporine is thought to be capable of increasing the risk of nephrotoxicity due to decreased synthesis of prostacyclin in the kidney. Accordingly, in the event of combination treatment, renal function must be monitored closely.
    • Captopril: Experimental studies indicate that ibuprofen counteracts the effect of captopril on sodium excretion.
    • Tacrolimus: Concomitant administration of NSAIDs and tacrolimus is thought to be capable of increasing the risk of nephrotoxicity due to decreased synthesis of prostacyclin in the kidney. Accordingly, in the event of combination treatment, renal function should be monitored closely.
    • Corticosteroids: Concomitant treatment gives rise to an increased risk of gastrointestinal ulceration or bleeding.
    • CYP2C9 Inhibitors: Concomitant administration of ibuprofen with CYP2C9 inhibitors may increase the exposure to ibuprofen (CYP2C9 substrate). In a study with voriconazole and fluconazole (CYP2C9 inhibitors) an increased S(+)-ibuprofen exposure by approximately 80 to 100% has been shown. Reduction of the ibuprofen dose should be considered when potent CYP2C9 inhibitors are administered concomitantly, particularly when high-dose ibuprofen is administered with either voriconazole or fluconazole.
    • Phenytoin: Plasmatic levels of phenytoin may be increased in the concomitant treatment with ibuprofen and therefore the risk of toxicity may increase.
    • Probenecid and sulfinpyrazone: Medicinal products that contain probenecid or sulfinpyrazone may delay the excretion of ibuprofen.
    • Herbal extracts: Ginkgo biloba may potentiate the risk of bleeding with NSAIDs.
    • Probenecid inhibits the binding of paracetamol to glucuronic acid, thus leading to a reduction in paracetamol clearance by a factor of approximately 2. In patients concurrently taking probenecid, the paracetamol dose should be reduced.
    • Enzyme-inducing drugs such as certain antiepileptics (phenytoin, phenobarbital, carbamazepine) decreased plasma AUC of paracetamol to approximately 60% in pharmacokinetic studies. Other substances with enzyme-inducing properties (i.e. rifampicin, Hypericum) could also result in decreased concentrations of paracetamol. In addition, the risk of liver damage during treatment with the maximum recommended dose of paracetamol is probably higher in patients who receive enzyme-inducing drugs.
    • Zidovudine may affect paracetamol metabolism and vice versa, which may add to the toxicity of both.
    • Anticoagulant drugs (warfarin) – dosage may require reduction if paracetamol and anticoagulants are taken for a prolonged period of time.
    • Severe hepatotoxicity at therapeutic doses or moderate overdoses of paracetamol has been reported in patients receiving isoniazid alone or with other drugs for tuberculosis
    • Paracetamol may affect the pharmacokinetics of chloramphenicol. Monitoring of chloramphenicol plasma levels is recommended if combining paracetamol with chloramphenicol injection treatment.
    • Ethyl alcohol potentiates paracetamol toxicity, possibly by inducing hepatic production of paracetamol-derived hepatotoxic products.
    • Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risks factors.
    Effects on laboratory tests:
    Intake of paracetamol can affect tests for uric acid using phosphotungstic acid and blood sugar tests using glucose-oxidase-peroxidase.
    See prescribing information for full details.

    Pregnancy and Lactation

    There is no experience of use of this product in humans during pregnancy. Because of the ibuprofen- component, this medicinal product is contraindicated during the third trimester of pregnancy.
    For ibuprofen
    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. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. From the 20th week of pregnancy onward, ibuprofen use may cause oligohydramnios resulting from foetal renal dysfunction. This may occur shortly after treatment initiation and is usually reversible upon discontinuation. In addition, there have been reports of ductus arteriosus constriction following treatment in the second trimester, most of which resolved after treatment cessation. Therefore, during the first and second trimester of pregnancy, ibuprofen should not be given unless clearly necessary. If ibuprofen 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 ibuprofen for several days from gestational week 20 onward. Ibuprofen 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 (with premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
    • renal dysfunction;
    the mother and the neonate, at the end of 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, this medicinal product is contraindicated during the third trimester of pregnancy.
    For paracetamol
    A large amount of data on pregnant women using paracetamol indicate neither malformative, nor foeto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.
    Paracetamol is excreted in breast milk but not in a clinically significant amount and available published data do not contraindicate breastfeeding as long as the recommended dosage is not exceeded.
    Ibuprofen and its metabolites can pass in very small amounts into breast milk. With therapeutic doses during short term treatment the risk for influence on infant seems unlikely.
    In light of the above evidences it is not necessary to interrupt breastfeeding for short-term treatment with the recommended dose of this product.
    The use of the product may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of the product should be considered.


    Liver injury and even failure can occur following paracetamol overdose. Symptoms of paracetamol overdose in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may proceed to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may develop in the absence of severe liver damage. Cardiac arrhythmias have been reported. Liver damage is possible in adults who have taken 10 g or more of paracetamol, due to excess quantities of a toxic metabolite.
    Symptoms include nausea, abdominal pain and vomiting, dizziness, convulsion and rarely, loss of consciousness. Clinical features of overdose with ibuprofen which may result are depression of the central nervous system and the respiratory system.
    In serious poisoning metabolic acidosis may occur.
    Prompt treatment is essential in the management of paracetamol overdose even when there are no obvious symptoms, because of the risks of liver injury, which presents after some hours or even days delay. Medical treatment is advised, without delay in any patient who has ingested 7.5 g or more of paracetamol in the preceding 4 hours. Gastric lavage should be considered. Specific therapy to reverse liver injury with an antidote such as acetylcysteine (intravenous) or methionine (oral) should be instituted as soon as possible.
    Acetylcysteine is most effective when administered during the first 8 hours following ingestion of the overdose and the effect diminishes progressively between 8 and 16 hours. It used to be believed that starting treatment more than 15 hours after overdose was of no benefit and might possibly aggravate the risk of hepatic encephalopathy. However, late administration has now been shown to be safe, and studies of patients treated up to 36 hours after ingestion suggest that beneficial results may be obtained beyond 15 hours. Furthermore, administration of intravenous acetylcysteine to patients who have already developed fulminant hepatic failure has been shown to reduce morbidity and mortality.
    An initial dose of 150 mg/kg of acetylcysteine in 200 mL 5% glucose is given intravenously over 15 minutes, followed by an I.V. infusion of 50 mg/kg in 500 mL 5% glucose over 4 hours and then
    100 mg/kg in 1 litre 5% glucose over 16 hours. The volume of I.V. fluids should be modified for children.

    Methionine is given orally as 2.5 g every 4 hours up to 10 g. Methionine treatment must be started within 10 hours after ingestion of paracetamol; otherwise, it will be ineffective and may exacerbate liver damage.
    Evidence of serious symptoms may not become apparent until 4 or 5 days following overdose and patients should be carefully observed for an extended period.
    Ibuprofen: Treatment should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable. Gastric lavage is only recommended within 60 minutes after ingestion of a life-threatening dose. Because the drug is acidic and is excreted in the urine, it is theoretically beneficial to administer alkali and induce diuresis. In addition to supportive measures, the use of oral activated charcoal may help to reduce the absorption and reabsorption of ibuprofen tablets.

    AFT Pharmaceuticals Ltd.
    Licence holder