Marcofen

Marcofen

Marcofen TM
Ibuprofen
Gastrointestinal risk: NSAlDs cause an increased risk of serious gastrointestinal
adverse event including inflammation. bleeding, ulceration and perforation of the
stomach or intestine v'hich can be fatal. These events can occur of any time during
use and without warnng symptoms. Elderly patients are at greater risk for serious
gastrointestinal events.
Cardiovascular Risk:
NSAlDs may cause an increased risk Of serious cardiovascular thrombotic events
myocardial infarction and stroke which can be fatal .This risk may increase
with duration of use .Patients with cardiovascular disease Or risk factors for
cardiovascular disease may be at greater risk.
NSAlDs is contraindicated for the treatment of peri-opcrativc pain in a setting of
raft (CABG SURGERY
corona arte
Coated Tablet: Each tablet contains 400 mg Ibuprofen.
Inactive ingredients: Maize starch, Povidone. Microcrystalline cellulose, colloidal
silicon dioxide. hydrogenated vegetable oil, crospovidone. carboxymethyl cellulose
sodium, opadry pink, hydroxypropyl methyl cellulose. titanium dioxide, glycerol.
Capsules SR: each capsule contains 400 mg Ibuprofen
Inactive ingredients: sugar spheres, Eudragit RLIOO, Povidone, Talc, Anhydrous colloidal
silica, Eudargit E 100 composition Of capsule shell: Body: Gelatin, Cap:Erythrosin E127.
Gelatin, Titanium dioxide .
Suspension: 100 mg | 5 ml Ibuprofen
Inactive ingredients: glycerine, microcrystalline Cellulose. carboxy methyl cellulose
sodium. Kaoline light, methyl paraben sodium salt, propyl paraben sodium salt, sodium
benzoate, polysorbate80, sorbitol 70%, saccharin sodium, citric acid monohydrate ,
Carmoisine red E122 Caramel flavour powder ,orange flavor, purified water.
Suppository: each suppository contains 100, 300 or 500 mg Ibuprofen
Inactive ingredients: polysorbate 60, hard fats.
Tablet, capsules, Suspension & Suppositories
Pharmaco'ogical Actign:
Ibuprofen is a propionic acid derivative with analgesic, anti-inflammatory and
anti-pyretic activity. The drug's therapeutic effects as an NSAID are thought to result
from its inhibitory effect On the enzyme cyclo-oxygenase, which results in a marked
reduction in prostaglandin synthesis.
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin
on platelet aggregation when they are dosed concomitantly. In one study. when a
single dose of ibuprofen 400mg was taken within 8 hours before or within 30 minutes
after immediate release aspirin dosing (81mg), a decreased effect of aspirin on the
formation of thromboxane or platelet aggregation occurred. However, the limitations
of these data and the uncertainties regarding extrapolation of ex vivo data to the
clinical situation imply that no firm conclusions can be made for regular ibuprofen use,
and no clinically relevant effect is considered to be likely for occasional ibuprofen use.
Ibuprofen is rapidly absorbed from the gastrointestinal tract, peak serum
concentrations occurring 1-2 hours after administration. The elimination half-life is
approximately 2 hours.
Ibuprofen is metabolised in the liver to two inactive metabolites and these, together
with unchanged ibuprofen, are excreted by the kidney either as such or as conjugates.
Excretion by the kidney is both rapid and complete. Ibuprofen is extensively bound
to plasma proteins
Indication:
Treatment of rheumatoid arthritis (including juvenile rheumatoid arthritis or
Still's Disease). ankylosing spondylitis, osteoarthritis and other non-rheumatoid
(seronegative) arthropathies.
In the treatment of non-articular rheumatic conditions, including frozen shoulder
(capulitis), bursitis. tendinitis, tendosynovitis, low back pain and soft-tissue injuries
such as sprains and strains.
As an analgesic in the relief of mild to moderate pain such as dysmenorrhoea, dental
and post-operative pain and for the symptomatic relief of headache including
migraine.
The suspension is indicated in short-term use for the treatment Of pyrexia in children
over one year Of age
adults
Tablet: The recommended dosage is 1200-1800 mg daily in 3-4 divided doses
preferably after food; some patients can be maintained on 600-1200 mg daily.
Suppository: 1 adult suppository 2-3 times daily
In severe or acute concitions the dose can be increased until the acute phase
is brought under control; the total daily dosage should not exceed 2400 mg in
divided doses.
Children:
Suspension: Daily dosage is 20 mg/kg of body weight in divided doses. This can be
achieved as follows using the suspension:

1-2 years: One 2.5 ml spoonful 50mg three to four times a day. 

3-7 years: One 5 ml spoonful (100 mg) three to four times a day. 

8-12 years: Two S ml spoonfuls (200 mg) three to four times a day. 

Not recommended for children under 7 kg weight. In juvenile rheumatoid arthritis up to 

40 mg/kg body weight daily in divided doses may be taken. 

Suppository: 

From 6 months to 6 years: 1 suppository 100 mg 3 times daily 

Above 6 years: 1 suppository 300 mg 3 times daily. 

Elderly: No special dpsage modifications, unless renal or hepatic function is impaired, 

in which case dosage should be assessed individually. Owing to the increased 

susceptibility of the elderly to side effects of NSAlD's, they should be recommended 

Only after other forms of treatment have been carefully considered. 

If an NSAID is considered necessary, the lowest dose should be used and the patient 

should be monitored for Gl bleeding for 4 weeks following initiation Of NSAID therapy. 

CQn!rH0dications: 

Marcofen is contraindicaæd in patients with hypersensitivity to the active substance 

or to any of the excipient! 

Marcofen should not be us ed in patients who have previously Shown hypersensitivity 

reactions (e.g. asthma. urtis•.aria, angioedema or rhinitis) after taking ibuprofen, 

aspirin or other NSAlDs. 

Marcofen is also contraindicated in patients with a history Of gastrointestinal 

bleeding or perforation. related to previous NSAID therapy. Marcofen should not be 

used in patients with active. or history of, recurrent peptic ulcer or gastrointestinal 

haemorrhage (two or more distinct episodes of proven ulceration or bleeding). 

Marcofen is contraindicated in patients with severe heart failure, hepatic failure 

and renal failure. 

Marcofen is contraindicated during the last trimester of pregnancy, 

Side Effects: 

Gastrointestinal disorders The most commonly observed adverse events are 

gastrointestinal in nature. Peptic ulcers, perforation or Gl bleeding, sometimes 

fatal, particularly in the elderly, may occur. Nausea. vomiting. diarrhoea, flatulence, 

constipation, dyspepsia, abdominal pain. melaena, haematemesis. ulcerative stomatitis, 

exacerbation of colitis and Crohn's disease have been reported following ibuprofen 

administration. Less frequently, gastritis has been Observed. Pancreatitis has been 

reported very rarely. 

Immune system disorders Hypersensitivity reactions have been reported following 

treatment with NSAlDs. These may consist of (a) non-specific allergic reaction and 

anaphylaxis, (b) respiratory tract reactivity comprising asthma, aggravated asthma, 

bronchospasm or dyspnoea. or (c) assorted skin disorders, including rashes of various 

types, pruritus. urticaria, purpura, angioedema and, more rarely, exfoliative and 

bullous dermatoses (including Stevens- Johnson syndrome, toxic epidermal necrolysis 

and erythema multiformc). 

Cardiac disorders and vasculardisorders: Oedema, hypertension and cardiac failure 

have been reported in association with NSAID treatment. Epidemiological data suggest 

that use of ibuprofen, particularly at high dose (2400 mg/ daily), and in long term 

treatment. may be associated with a small increased risk of arterial thrombotic events 

such as myocardial infarction or stroke. 

Other adverse events reported less commonly and for which causality has not 

necessarily been established includes: 

Blood and lymphatic system disorders: Thrombocytopenia, neutropenia, 

agranulocytosis, aplastic anaemia and haemolytic anaemia. 

Psychiatric disorders: Depression. confusional state, hallucination 

Nervous system disorders: Optic neuritis, headache, paraesthesia, dizziness. 

somnolence 

Aseptic meningitis (especially in patients with existing autoimmune disorders, such as 

systemic lupus erythematosus and mixed connective tissue disease) with symptoms Of 

stiff neck, headache, nausea, vomiting. fever or disorientation. 

Eye disorders: Visual disturbance 

Ear and labyrinth disorders Tinnitus, vertigo 

Hepatobiliory disorders: Abnormal liver function, hepatic failure, hepatitis and 

jaundice. 

Skin and subcutaneous tissue disorder,: Bullous reactions. including Stevens-Johnson 

syndrome and toxic epidermal necrolysis (very rare), and photosensitivity reaction. 

Renal and urinary disorders: Impaired renal function and toxic nephropathy in various 

forms. including interstitial nephritis, nephrotic syndrome and renal failure. 

General disorders and administration site conditions: Malaise, fatigue. 

Drug Interaction: 

Care should be taken in patients treated with any of the following drugs as interactions 

have been reported in some patients. 

Antihypertensive: Reduced antihypertensive effect. 

Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity 

of NSAlDs. 

Cardiac glycosides: NSAlDs may exacerbate cardiac failure, reduce GFR and increase 

plasma cardiac glycoside levels. 

Lithium: Decreased elimination of lithium. 

Methotrexate: Decreased elimination of methotrexate. 

Ciclosporin: Increased risk Of nephrotoxicity. 

Mifepristone: NSAlDs should not be used for 8-12 days after mifepristone 

administration as NSAlDs can reduce the effects of mifepristone. 

Other analgesics and cyc100iygenase-2 selective inhibitors: Avoid concomitant use 

of two or more NSAlDs, including Cox-2 inhibitors. as this may increase the risk Of 

adverse effects. 

Aspirin: As with other products containing NSAlDs, concomitant administration 

of ibuprofen and aspirin is not generally recommended because of the potential of 

increased adverse effects. 

Experimental data suggest that ibuprofen may inhibit the effect of low doseaspirin 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 use. 

Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding with NSAlDs. 

Anticoagulants: NSAlDs may enhance the effects Of anticoagulants, such as warfarin. 

Quinolone antibiotics: Animal data indicate that NSAlDs can increase the risk Of 

convulsions associated with quinolone antibiotics. Patients taking NSAlDs and 

quinolones may have an increased risk of developing convulsions. 

Anti-platelet agents and selective serotonin reuptake inhibitors (SSR15J: Increased risk of 

gastrointestinal bleeding with NSAlDs. 

Tacrolimus: Possible increased risk of nephrotoxicity when NSAlDs are given With 

tacrolimus. 

Zidovudine: Increased risk of haematologicai toxicity when NSAlDs are given with 

zidovudine. There is evidence of an increased risk ofhaemarthroses and haematoma in 

HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen. 

Amino glycosides: NSAlDs may decrease the excretion Of aminoglycosides. 

Herbal extracts. Ginkgo biloba may potentiate the of bleeding with NSAlDs. 

Pregnancy 

Congenital abnormalities have been reported in assoéiation with NSAID administration 

in man; however, these are low in frequency and do not appear to follow any discernible 

pattern. In view of the known effects of NSAlDs on the foetal cardiovascular system 

(risk of closure of the ductüs arteriosus), use in the last trimester Of pregnancy is 

contraindicated. The onset of labour may be delayed and the duration increased with 

an increased bleeding tendency in both mother and child. NSAlDs should not be used 

during the first two trimesters of pregnancy or labour unless the potential benefit to 

the patient outweighs the potential risk to the foetus. 

Lactation 

In the limited studies so far available, NSAlDs can appear in the breast milk in very low 

concentrations. NSAID% should, if possible, be avoid'd"hen breastfeeding, 

Undesirable effects may be minimised by using thebwest effective dose for the 

shortest duration necessary to control symptoms. 

Patients with rare hereditary problems of fructose mtolerance, glucose-galactose 

malaabsorption or sucrasc-isomaltase insufficiency should not take this medicine, 

As with Other NSAlDs, ibuprofen may mask the signs of infection. 

The use of Marcofen with concomitant NSAlDs, inciuding cyclooxygenase-2 selective 

inhibitors, should be avoided due to the potential for additive effects. 

Elderly 

The elderly have an increased frequency Of adverse reactions to NSAlDs, especially 

gastrointestinal bleeding and perforation. which may be fatal. 

Gastrointestinal bleeding, ulceration and perforatiån 

Gl bleeding, ulceration or perforation, which Can be fatal, has been reported with all 

NSAlDs at anytime during treatment, with or without warning symptoms Or a previous 

history of serious Gl events. 

The risk of Gl 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 doge avaiable. 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 aspirin, or other drugs likely to increase 

gastrointestinal risk. 

Patients with a history of gastrointestinal disease, particularly when elderly. should 

report any unusual abdominal symptoms (especially gastrointestinal 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 Gl bleeding or ulceration occurs in patients receiving Marcofen, the treatment 

Should be withdrawn. 

NSAlDs should be given with care to patients with a history Of ulcerative colitis or 

Crohn•s disease as these conditions may be exacerbated. 

Respiratory disorders 

Caution is required if Marcofen "ministered to patients suffering from. or with a 

previous history of, bronchial asthma since NSAlDs have been reported to precipitate 

bronchospasm in such patients, 

Cardiovascular, renal and hepatic impairment 

The administration of an NSAID 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. Renal function should bc monitored in these patients. 

Marcofen should be given with care to patients with a history Of heart failure 

or hypertension since oedema has been reported in association with ibuprofen 

administration. 

Cardiovascular and cerebrovasculor effects 

Appropriate monitoring and advice are required for patients with a history of 

hypertension and/or mild to moderate congestive heart failure as fluid retention and 

oedema have been reported in association with NSAID therapy. 

Epidemiological data suggest that use of ibuprofen, particularly at a high dose 

(2400 mg/ daily) and in long term treatment, may be associated with a small increased 

risk of arterial thrombotic events such as 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 arterial thromboticevents, particularly 

myocardial infarction. 

Patients with uncontrolled hypertension, congestive heart failure, established 

ischaemic heart disease, peripheral arterial disease. and/or cerebrovascular disease 

should only be treated with ibuprofen after careful consideration. Similar consideration 

should be made before initiating longer-term treatment Of patients with risk factors for 

cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking). 

Renal effects 

Caution should be used when initiating treatment with ibuprofen in patients with 

considerable dehydration. 

As with other NSAlDs, long-term administration of ibuprofen has resulted in renal 

papillary necrosis and other renal pathologic changes. Renal toxicity has also been 

seen in patients in whom renal prostaglandins have a compensatory role in the 

maintenarce of renal perfusion. In these patients. administration of an NSAID may 

cause a dose-dependant reduction in prostaglandin formation and, secondarily. in renal 

blood flow. which may precipitate overt renal decompensation. Patients at greatest risk 

of this reaction are those with impaired renal function. heart failure, liver dysfunction, 

those taking diuretics and ACE inhibitors and the elderly. Discontinuation of NSAID 

therapy is usually followed by recovery to the pre-treatment state. 

SIE and mixed connective tissue disease 

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue 

disorders there may be an increased risk of aseptic meningitis 

Dermatological effects 

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 NSAlDs. Patients appear to be at highest risk of 

these reactions early in the course Of therapy, the Onset of the reaction occurring 

within the first month of treatment in the majority of cases. Marcofen should be 

discontinued at the first appearance of skin rash, mucosal lesions, or any other sign 

of hypersensitivity. 

Haematological effects 

Ibuprofen. like other NSAlDs, can interfere with platelet aggregation and has been 

shown to prolong bleeding time in normal subjects. 

Asceptic meningitis 

Aseptic möngitis has been observed on rare occasions in patientson ibuprofen 

therapy. Ahhough it is probably more likely to occur in patients with systematic lupus 

erythematosus and related connective tissue diseases, it has been reported in patients 

who do not have an underlying chronic disease. 

Impaired female fertility 

The use of Marcofen 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 Marcofen should be considered. 

Marcofen 400 mg Tablet: Carton box contains two strips of 10 tablets and Leaflet 

Marcofen SR Capsule: Carton box contains One strip Of 10 capsules and Leaflet 

Marcofen suppositories 100, 300 and 500 mg: Carton box contains one strip Of 

5 supp, and Leaflet 

Marcofen suspension 100 mg: Carton box contains glass bottle of 120 ml and Leaflet 

Storage: 

For Tablet, Capsule and Suppository. See outer pack. 

Marcofen Suspension: Store below 250C. Protect from light. 

Manufaguxc 

Tablets, capsules and suspension: 

Manufactured by: GlaxoSmithKline El Salam City -Cairo 

Suppositories: 

Manufactured by: SmithKline Beecham el Haram . Giza for GlaxoSmithKline 

sk 

GlaxoSmithKline 

CP219/08