Gofex

Clear, colourless, oily liquid filled in 20 minim, oblong, green, transparent soft gelatin shell capsules.
Each softgel capsule contains: Solubilized Ibuprofen Eq to Ibuprofen 400 mg (present as free acid and potassium salt).
Excipients/Inactive Ingredients: Polyethylene glycol 600, potassium hydroxide, purified water, gelatin, sorbitol, glycerin, FD&C green no 3.

Pharmacotherapeutic group: Anti-inflammatory and anti-rheumatic products, non-steroids, propionic acid derivatives. Ibuprofen is a synthetic analgesic-anti-inflammatory drug with a marked antipyretic action.
Pharmacology: Pharmacodynamics: Mechanism of action: Ibuprofen is the first phenylpropionic acid derivative. It is a prostaglandin synthetase inhibitor with analgesic, antipyretic and anti-inflammatory properties. It possesses a nonnarcotic analgesic activity. The mechanism of action of ibuprofen (insitu formation of L-arginine salt) is linked to the reversible inhibition of the COX enzyme, responsible for conversion of arachidonic acid into cyclic endoperoxides, hence reducing the synthesis of thromboxane (TXA2), prostacyclins (PGI2) and prostaglandins (PG).
Pharmacokinetics: On oral application, ibuprofen is partly absorbed in the stomach and then completely in the small intestine. After absorption, ibuprofen is conjugated to plasma-proteins for about 99% and is mainly distributed throughout the plasma compartment. It diffuses slowly into the synovial spaces and is eliminated more slowly from these spaces than it is from the plasma. Ibuprofen is metabolized in the liver mainly by hydroxylation and carboxylation of the isobutyl group. The metabolites have no known pharmacological activity. The plasma half-life is 1-2 hours. Over 90% of dosage can be found in the urine as metabolites and their conjugates. Less than 1% is excreted unchanged in the urine.
Bioequivalence Study Result: Bioequivalence study was carried out on Gofen soft capsules 400 mg (produced by Mega Lifesciences Ltd., Thailand) compared with Nurofen 400 caplets (produced by Reckitt Benckiser Healthcare Manufacturing Ltd., Thailand) with an open label balanced, randomized, two-treatment, two-period, two-sequence, single dose, crossover study design, in 28 healthy subjects in fasting conditions. Study results showed that test drug is bioequivalent to reference drug with GMR AUC0-t, AUC0-~ and Cmax value 95.72%, 93.93% and 119.81% respectively with a 90% CI values 90.98-100.71%, 90.02-98.02% and 109.73-130.82%.
Results of Comparative Dissolution Test (CDT) carried out between test drug (Gofen soft capsules 400 mg) and reference drug (Nurofen caplets 400 mg) at 3 pH (0.1 N HCl medium, pH 4.5 acetate buffer, and phosphate buffer pH 6.8) are 94.95%, 62.77%, and 69.78% respectively. The results at these three pH showed that the two products are similar with F2 value ≥50.0.
Results of Comparative Dissolution Test (CDT) carried out between comparator used in the BE study (Nurofen caplet 400 mg) and innovator approved in Indonesia (Spedifen tablet 400 mg) in 3 pH (medium HCl 0.1 N, acetate buffer pH 4.5, and phosphate buffer pH 6.8) are 79.51%, 56.30% and 64.24% respectively. The results on these three pH levels showed that the two products are similar with F2 value ≥50.0.

For relieving the pain of various etiology: headache, pain after tooth extraction, and postoperative pain, as well as for the treatment of primary dysmenorrhea.
For the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis, as well as for the musculoskeletal and traumatic alterations implying pain and inflammation.

Dosage for adults: The main recommended posology is 1,200 mg/day, divided into 3-4 single administrations. Should gastric disturbances appear after drug ingestion, then the administration can be performed by drinking concomitantly some milk or during meals.
In case of rheumatoid arthritis, a higher dosage may be required but, in any case, it is recommended not to exceed 2,400 mg Ibuprofen a day, by considering that the lowest possible effective dose is to be administered.
In case of primary dysmenorrhea, the recommended dose is 400 mg every 4 hours up to pain relief, always considering the lowest possible effective dosage.
For elderly patients, the posology is to be established by the physician, as a possible usual dose reduction may be needed, in case of kidney failure, the dosage must be adequately adjusted, being the drug eliminated preferably through renal excretion.

Symptoms: In general, overdose symptoms include nausea, gastralgia, vomiting (blood) and diarrhoea (blood), dizziness, spasms, nystagmus and diplopia, headache and tinnitus. In case of severe intoxication also renal function disorders, hypotension, decrease of consciousness and coma (it is not clear whether the renal function disorder is caused by the intoxication or by the concurrent hypotension). In serious poisoning metabolic acidosis may occur.
Management of overdose: There is no specific antidote for ibuprofen.
The stomach should be emptied as soon as possible. If possible, the patient should vomit. If the patient is unconscious, gastric lavage and correction of severe electrolyte abnormalities should be considered.

Hypersensitivity to the active substance "ibuprofen" or to any of the excipients of this medicinal product. (See Description).
History of hypersensitivity reactions (e.g. bronchospasm, asthma, rhinitis or urticaria) in response to acetylsalicylic acid (ASA) or other non-steroidal anti-inflammatory drugs (NSAIDs).
History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Other active bleeding like cerebrovascular bleedings or colitis ulcerosa.
Severe kidney and/or liver insufficiency.
Hemorrhagic diathesis.
Third trimester of pregnancy (see Use in Pregnancy & Lactation).
Severe heart failure (NYHA Class IV).

Cardiovascular Risk: NSAIDs 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.
NSAIDs is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
Gastrointestinal Risk: NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events.

Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see Dosage & Administration and Gastrointestinal Risk and Cardiovascular Risk under Warnings).
GI Effects: The use of ibuprofen with Concomitant NSAIDs, including COX-2 selective inhibitors should be avoided.
Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation, which may be fatal (see Dosage & Administration).
Gastrointestinal bleeding, ulceration and perforation: 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 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 hemorrhage or perforation (see Contraindications), 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 aspirin, or other drugs likely to increase gastrointestinal risk (see Interactions).
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 acetyl salicylic acid (see Interactions). When GI bleeding or ulceration occurs, the treatment should be withdrawn. NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated (see Side Effects).
Cardiovascular and cerebrovascular effects: Appropriate monitoring and advice are required for patients with a history of hypertension and or mild to moderate congestive heart failure. Fluid retention, hypertension and oedema have been reported in association with NSAIDs therapy.
Clinical studies suggest that use of ibuprofen, particularly at a high dose (2,400 mg/day) may be associated with a small increased risk of arterial thrombotic event (for example myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g. ≤1,200 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 (2,400 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 (2,400 mg/day) are required.
Severe skin reactions: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Steven-Johnson's syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see Side Effects). Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Ibuprofen-containing products should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Masking of symptoms of underlying infections: Ibuprofen 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 Ibuprofen 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.
Other effects: Caution is required in patients with coagulation disorders and liver, cardiac or kidney insufficiency. Caution should be used when initiating treatment with ibuprofen in patients with considerable dehydration.
Risks of long-term habitual use of analgesic are headache and analgesic nephropathy.
Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma or allergic disease.
Caution is required in patients with systemic lupus erythematosus or other collagen diseases. 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 withdrawal of treatment.
Patients who experience visual disturbances during ibuprofen therapy should discontinue the treatment and have an ophthalmologic examination. NSAIDs may produce an increase of liver function test results.
Effect on ability of driving and operating machine: Dizziness and headache have been reported which may affect the patient's ability to drive or to operate machinery. Single administration or short term use of ibuprofen does not usually warrant the adoption of any special precautions. Therefore, GOFEN has minor influence on these abilities.

Pregnancy: Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. During the first and second trimester of pregnancy, GOFEN should not be given unless clearly necessary. If GOFEN 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. Consequently, GOFEN is contraindicated during the third trimester of pregnancy (see Contraindications).
Lactation: Ibuprofen and its products of decomposition/metabolites are excreted in human milk, but at therapeutic doses of GOFEN no effects on the breastfed newborns/infants are anticipated. As harmful effects on the infant are not yet known, it is not generally necessary to interrupt breast-feeding for short-term treatment with recommended dose for mild to moderate pain and fever.
Fertility: If Ibuprofen is used by a woman attempting to conceive the dose should be kept as low and duration of treatment as short as possible.

Undesirable effects are primary linked to the pharmacological effect of ibuprofen on prostaglandin synthesis. The most commonly reported adverse events effect the gastrointestinal tract, ranging from nausea and dyspepsia to serious bleeding or activation of peptic ulcer (see Precautions).
Bullous reaction including Steven-Johnson's syndrome and toxic epidermal necrolysis were observed very seldom.
Oedema, hypertension, and cardiac failure have been reported in association with NSAIDS treatment. Clinical studies suggest that use of ibuprofen, particularly at high dose (2,400 mg/day) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infraction or stroke) (see Precautions).
In the table as follows adverse reactions are listed by system organ class, and frequency very common (more than or equal to 1/10), common (21/100 to less than 1/10), uncommon (21/1,000 to 1/100), rare (21/10,000 to less than 1/1,000), very rare (less than 1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See table.)


Click on icon to see table/diagram/image


Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to.
Email: pv-center@pom.go.id.
Phone: +62-21- 4244691 Ext. 1079.
Website: http://e-meso.pom.go.id/.

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 (see Pharmacology: Pharmacodynamics under Actions).
Diuretics: The efficacy of furosemide and thiazide diuretics can be decreased, probably due to sodium retention related to an inhibition of prostaglandin synthesis in the kidneys.
Corticosteroid: Increase risk of gastrointestinal ulceration or bleeding (see Precautions).
Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see Precautions).
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (see Precautions).
Anti-hypertensives agents: Ibuprofen may diminish the effects of antihypertensives.
Consequently, the concomitant use of NSAIDs and ACE Inhibitors or beta-blocking agents may be associated with a risk of acute renal failure.
Digoxin, phenytoin, lithium: In the literature individual cases of increase plasma levels of digoxin, phenytoin and lithium due to ibuprofen have been described.
Other non-steroid anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 selective inhibitors: Ibuprofen (like other NSAIDS) should be used with caution in combination with acetylsalicylic acid or other NSAIDs and systemic corticosteroids: This may increase the risk of adverse drug reactions in the gastrointestinal tract.
Methotrexate: Ibuprofen can increase methotrexate plasma levels.
Zidovudine: Concurrent treatment of zidovudine and ibuprofen can increase the risk of haemarthrosis and haematoma in HIV (+) haemophilic patients.
Tacrolimus: Concurrent use of ibuprofen and tacrolimus can increase the risk of nephrotoxicity, due to the reduction of the renal prostaglandins synthesis.
Hypoglycaemics agent: Ibuprofen increases hypoglycemic effects of oral hypoglycemic agents and insulin. It may be necessary to adjust the dosage.
Cyclosporine: Concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) may result in increased risk of cyclosporine nephrotoxicity effect.
Voriconazole or Fluconazole: Concurrent use of ibuprofen may result in increased ibuprofen exposure and plasma concentration.
Mifepristone: Concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) may result in increased exposure to the NSAID. A decrease in the efficacy of mifepristone can theoretically occur due to the antiprostaglandin properties of NSAIDs. Studies on the effect of single or repeated ibuprofen administration starting on the day prostaglandin administration (or as needed) did not find evidence of an adverse influence on the action of mifepristone, nor or the overall clinical efficacy of the pregnancy termination protocol.
Quinolone antibiotics: Concurrent use of non-steroidal use of non-steroidal anti-inflammatory drugs (NSAIDs) may result in an increased risk of seizures.
Herbal Extract: Gingko biloba may potentiate the risk of bleeding with NSAIDS.
Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides.
Interactions with diagnostic test results: Bleeding time (may prolong bleeding time until 1 day after discontinuation of therapy).
Serum glucose concentration (may decrease).
Creatinine Clearance (may decrease).
Haematocrit or haemoglobin (may decrease).
BUN, serum creatinine concentration and kaliemia (may increase).
Liver function test (may occur elevation of transaminases).

Do not use the product if there are any significant changes in appearance of the capsules.

Store below 30°C in a dry place, away from direct sunlight.
Shelf Life: Two years from manufacturing date.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AE01 - ibuprofen ; Belongs to the class of propionic acid derivatives of non-steroidal antiinflammatory and antirheumatic products.

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