Each film – coated tablet contains 400 mg ibuprofen (as L-arginine).
Ibuprofen is a synthetic analgesic and anti-inflammatory agent with a marked antipyretic effect.
Mechanism of action
Chemically, it represents the progenitor of phenylpropionic derivatives with anti-inflammatory activity. Its analgesic activity is not narcotic. Ibuprofen is a powerful prostaglandin synthesis inhibitor and exerts its activity by inhibiting its synthesis peripherally.
The mechanism of action of ibuprofen (in situ formation of L-arginine salt) is linked to the reversible inhibition of the COX enzyme, responsible for the conversion of arachidonic acid into cyclic endoperoxydes, hence reducing the synthesis of thromboxane (TXA2), prostacyclines (PGI2) and prostaglandins (PG).
In dental pain a meaningful pain relief occurs within 25-30 minutes.
In primary dysmenorrhea 82% of patients reported a marked decrease in pain intensity at 15 minutes and 98% at 30 minutes after oral administration of 600 mg.
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 400 mg was taken within 8 hours before or within 30 minutes after immediate release aspirin dosing (81 mg), a decreased effect of ASA on the formation of thromboxane or platelet aggregation occurred.
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 the occasional ibuprofen. (See Interaction with other Medicinal Products and other Forms of Interaction.
Ibuprofen arginine (FASPIC), due to the presence of basic amino acid such as arginine, allows ibuprofen solubilization and assures an excellent and prompt absorption of the active ingredient after oral administration.
Studies on man show that ibuprofen arginine (FASPIC), a new ibuprofen preparation, enables prompter drug absorption with respect to other traditional pharmaceutical forms (the peak concentration appears earlier) and with a serum bioavailability higher in the first hour following drug administration.
After oral administration, Ibuprofen arginine (FASPIC) is rapidly absorbed by the GI tract. Maximal ibuprofen plasma levels by approximately 40 ug/mL and 60 ug/mL are achieved at approximately 35 minutes after administration of Ibuprofen arginine (FASPIC) 400 mg and 600 mg tablet.
The peak plasma concentration is reached approximately within 15-30 minutes, and plasma levels are attained within 5 – 10 minutes after oral administration. This feature is particularly advantageous in clinical conditions (e.g. intense pain) where a prompt analgesic effect is required.
Concomitant administration with food does not influence the extent of absorption but delays the absorption of approximately 1 hour, which results in a lower Cmax (approx. 50%).
After absorption, ibuprofen is conjugated to plasma proteins for about 99% and is mainly distributed throughout the plasma compartment. It diffuses slowly into 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.
Ibuprofen arginine administration did not result in the accumulation of either the rug or its metabolites since excretion is practically complete after 24 hours.
Ibuprofen shows non-linear kinetics in as much as total plasma AUC increases less than proportionately with the given dose. Non-linearity is attributed to saturation of plasma protein binding.
There is no evidence of accumulation in elderly or retention in specific body compartments. Therefore no dose adjustment is proposed.
Mild/moderate renal impairment does not appear to cause any elongation of the plasma elimination half-life. Patients with end stage renal disease should not be taking ibuprofen as there would be an expected increase in risk of systemic accumulation.
There is little evidence of alterations in plasma pharmacokinetics in patients with mild hepatic disease. Patients with severe liver diseases should not be taking ibuprofen as there would be an expected increase in risk of systemic accumulation.
Pharmacokinetic of ibuprofen in children aged 12 years onwards is similar to that of adults.
The faster absorption of ibuprofen (in situ formation of L-arginine salt) with respect to ibuprofen per se results in a faster analgesic activity.
Preclinical Safety Data
Toxicological tests performed in various animal species by different routes of administration demonstrated that ibuprofen is well tolerated and did not show teratogenic effects. It must however be pointed out that administration of NSAIDs to pregnant rats may induce a restriction of Botallo’s duct.
Ibuprofen arginine (FASPIC) 400 mg Film-Coated Tablet is indicated for the symptomatic relief of mild to moderate pain with inflammation.
- Pain treatment: headache, dental pain including pain after tooth extraction, primary dysmenorrhea, neuralgia, joint and muscular pains, episiotomy and post-partum pain, post-operative pain, pain due to small lesions or pain brought about by trauma
- In the symptomatic treatment of chronic painful and inflammatory rheumatic conditions due to rheumatoid disease, both with articular and extra-articular involvement: rheumatoid arthritis, ankylosing spondylitis, Still’s disease
- Degenerative rheumatic forms: osteoarthritis (cervical, dorsal and lumbar arthrosis, gonarthritis, coxarthritis, polyarthritis, etc.)
- Extra-articular rheumatic forms: tendonitis, fibrositis, bursitis, myalgia, lumbago, scapulohumeral periarthritis, ischialgia, radiculoneuritis
DOSAGE AND ADMINISTRATION
The use of the product is restricted to adult patients only.
Ibuprofen arginine (FASPIC) 400 mg Film-Coated Tablets: 2 – 4 tablets daily, according to the advice of the physician.
The maximum daily dose must not exceed 1600 mg per 24 hours.
For rheumatic pain, it is suggested to administer the first daily dose in the morning before meals in order to improve the joint’s rigidity while the following doses are to be administered during or after meals.
Patients should discuss with their doctors the risks and benefits of using NSAIDs and the importance of using the lowest effective dose for the shortest duration possible if treatment for NSAIDs is required.
Do not take this drug continuously for more than 10 days unless prescribed by the physician.
In the treatment of elderly patients, the dosage must be carefully established by the physician, taking into consideration the possible reduction of the aforementioned dosage.
Precautions to be taken before handling or administering the medicinal product
If one or more dose(s) is (are) missed, it is advisable to take the lowest recommended dose at the earliest convenience. The interval between doses should be no shorter than 4 hours.
Ibuprofen must not be administered in the following cases:
- Known hypersensitivity to the active ingredient, to other NSAIDs or to any of the components of the product
- Contraindicated in patients with history of hypersensitivity to ASA or any other NSAIDs
- NSAIDs are contraindicated in patients with previous or active peptic ulceration
- Use with caution in patients with cardiac, liver and renal disease. Dose adjustment like using the lowest effective dose and monitoring of renal and liver functions should be instituted.
- Patients who experienced asthma, urticarial, angioneurotic edema or other allergic reactions after using compounds with similar action (e.g. acetylsalicylic acid or other NSAIDs)
- Gastrointestinal bleeding
- Intestinal inflammatory disease
- Active, or history of recurrent peptic ulcer/haemorrhate (two or more distinct episodes of proven ulceration or bleeding)
- Severe hepatic disease
- Severe renal failure
- In case of systemic lupus erythematosus and collagen diseases, consult the attending physician before using Ibuprofen arginine (FASPIC)
- Other active bleeding like cerebrovascular bleedings or colitis ulcerosa
- Patients with hemorrhagic diathesis or other coagulation alteration
- Pregnancy (see Pregnancy and Lactation)
- Severe heart failure
SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms. (See Dosage and Administration and Gastrointestinal and Cardiovascular Risks below)
- GI effects: The concomitant use of Ibuprofen arginine (FASPIC) with concomitant NSAIDs including cyclooxygenase-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
- Gastrointestinal bleeding, ulceration and perforation: GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at anytime 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 those patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk.
- Special caution is recommended in patients with pre-existing gastrointestinal disturbances, previous gastric or duodenal ulcer, ulcerative colitis, Crohn’s disease and alcoholism. Due to the possible onset of digestive problems, especially gastrointestinal bleeding, an accurate monitoring of these patients is required during administration of ibuprofen or other non-steroidal anti-inflammatory drugs.
- 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 antiplatelet agents such as acetylsalicylic acid (See Interaction with other Medicinal Products and other forms of Interaction)
- When GI bleeding or ulceration occurs, the treatment should be withdraw.
- 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 edema have been reported in association with NSAIDs therapy.
- Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at a high dose (2400 mg daily) and in a long term treatment 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. < 1200 mg daily) is associated with an increased risk of arterial thrombotic events.
- Patients with 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 be made before initiating longer –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.
- Ibuprofen arginine (FASPIC) must be administered with extreme caution in patients with a history of heart failure, hypertension and pre-existing edema of any nature and in patients with hepatic or renal impairment.
- Skin reactions
- 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 NSAIDs (See Adverse Events). 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 arginine (FASPIC) should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
- Other effects
- 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
- Caution is likewise required in patient with previous episodes of bronchospasm especially following the use of other drugs.
- As a precautionary measure, all patients under long term treatment with ibuprofen must be subjected to a regular monitoring of the renal, hepatic and hematologic function by providing regular blood profile.
- Ibuprofen, like other NSAIDs, can prolong bleeding time and therefore must be used with due caution in patients with blood coagulation disorders.
- Since visual or ocular alterations, though rare, were reported during treatment with ibuprofen, it is recommended to discontinue the treatment in case of any onset of visual disturbances and an ophthalmologic examination must be performed.
- The use of Ibuprofen arginine (FASPIC) as well as any other prostaglandin synthesis and cyclooxygenase inhibitors is not recommended in women with pregnancy plans. This may cause impairment of female fertility with an effect on ovulation. Administration of the drug must be suspended in women with fertility problems or are currently undergoing fertility investigations.
- Ibuprofen may mask the objective and subjective signs of an infection. In isolated cases an exacerbation of infective inflammations (e.g. development of necrotizing fasciitis) has been described in temporal connection with the use of NSAIDs. Therapy with ibuprofen in patients with an infection should therefore be used with care.
- Caution is required in patients with systemic lupus erythematosus or other collagen diseases
- NSAIDs may produce an increase of liver function test results
INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION
- Acetylsalicylic acid (low dose): experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin 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 low0dose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered to be likely for occasional ibuprofen use.
- Anticoagulants: NSAIDs may enhance the effect of anti-coagulants, such as warfarin
- Generally, NSAIDs must be used with caution when they are concomitantly administered with other drugs that may increase the risk of gastrointestinal ulcer and bleeding or renal impairment.
- Notable interactions involving NSAIDs include: enhancement of the effects of oral anticoagulants (especially by azapropazone and phenylbutazone) and increased plasma concentrations of lithium, methotrexate and cardiac glycosides.
- The risk of nephrotoxicity may be increased if given with ACE inhibitors, ciclosporin, tacrolimus, or diuretics. Effects on renal function may lead to reduced excretion of some drugs. There may also be an increased risk of hyperkalemia with ACE inhibitors and potassium-sparing diuretics.
- The antihypertensive effects of some antihypertensives including ACE inhibitors, beta blockers and diuretics may be reduced.
- Convulsions may occur due to an interaction with quinolones.
- NSAIDs may enhance the effects of phenytoin and sulfonylurea antidiabetics.
- The effects of NSAIDs might be enhanced by use with moclobemide.
- The concomitant use of more than one NSAID (including aspirin) should be avoided because of the increased risk of adverse effects.
- The risk of gastrointestinal bleeding and ulceration associated with NSAIDs is increased when used with corticosteroids, the antiplatelets clopidogrel and ticlopidine, or possibly, alcohol, bisphosphonates or oxpentifylline (pentoxifylline).
- There may be an increased risk of haematotoxicity during concomitant use of zidovudine and NSAIDs; blood counts 1 to 2 weeks after starting use together are recommended.
- Ritonavir may increase the plasma concentrations of NSAIDs.
- The manufacturer of mifepristone advises that NSAIDs or aspirin should be avoided for 8 to 12 days after mifepristone use because of a theoretical risk that these prostaglandin synthetase inhibitors may alter the efficacy of mifepristone.
- There have been occasional reports of increased adverse events when NSAIDs were given with misoprostol although such combinations have sometimes been employed to decrease the gastrointestinal toxicity of NSAIDs.
- Cyclosporine: concurrent use of NSAIDs may result in an increased risk of cyclosporine nephrotoxicity effect
- Voriconazole or fluconazole: concurrent use of ibuprofen may result in increased ibuprofen exposure and plasma concentration
- Herbal extracts: Ginkgo biloba may potentiate the risk of bleeding with NSAIDs
- Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides
Interactions with diagnostic results:
- Bleeding time (may prolong bleeding time until 1 day after discontinuation of therapy)
- Serum glucose concentrations (may decrease)
- Creatinine clearance (may decrease)
- Haematocrit or haemoglobin (may decrease)
- BUN, serum creatinine concentrations and kaliemia (may increase)
- Liver function test (may occur elevation of transaminases)
FERTILITY, PREGANCY AND LACTATION
The use of the product during pregnancy, lactation and children is not recommended.
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies raise concern about an increased risk of miscarriage and of cardiac malformations and gastroschisis in the newborns after the use of a prostaglandin synthesis inhibitor in the early phase of pregnancy. The absolute risk on cardiac malformation was increased from less than 1% to about 1.5%. It is assumed that the risk increases with dose and duration of therapy. Administration of prostaglandin synthesis inhibitors to animals resulted in an increased pre- and post-implantation loss and embryo fetal lethality. Moreover, an increased incidence of various malformations, including cardiovascular defects, has been reported in animals receiving prostaglandin synthesis inhibitors during the period of organogenesis. During the first and second trimester of pregnancy, Ibuprofen arginine (FASPIC) should not be given unless clearly necessary. If Ibuprofen arginine (FASPIC) 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.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to:
- Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
- Renal dysfunction, which may progress to renal failure with oligo-hydroamniosis
And the mother and the child, at the end of pregnancy, may be exposed to:
- Possible prolongation of bleeding time, an anti-aggregating effect which may occur even after very low doses
- Inhibition of uterine contractions during the third trimester of pregnancy
Consequently, Ibuprofen arginine (FASPIC) is contraindicated during the third trimester of pregnancy
Ibuprofen and its products of decomposition/metabolites are excreted in human milk, but at therapeutic doses of Ibuprofen arginine (FASPIC) no effects on the breastfed newborns/infants are anticipated. As harmful effects on the infant are not known, it is not generally necessary to interrupt breast-feeding for short-term treatment with the recommended dose for mild to moderate pain and fever.
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.
EFFECTS ON THE ABILITY TO DRIVE AND USE MACHINERY
Driving and use of machinery must be avoided in patients who, during ibuprofen treatment, experience symptoms such as dizziness, vertigo, visual alterations or other central nervous system disturbances.
Single administration or short term use of ibuprofen does not usually warrant the adoption of any special precautions. Therefore, Ibuprofen arginine (FASPIC) has minor influence on these abilities.
The most commonly reported adverse events affect the gastrointestinal tract, ranging from nausea and dyspepsia to serious bleeding or activation of peptic ulcer.
Bullous reaction including Stevens-Johnson syndrome and toxic epidermal necrolysis where observed very seldom.
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 dose (2,400 mg daily), and in long term treatment may be associated with a slightly increased risk of arterial thrombotic events (e.g. myocardial infarctions or stroke).
In the table below adverse reactions are listed by system organ class, and frequency (very common (>1/10), common (>1/100 to < 1/10), uncommon (>1/1000 to <1/100), rare (>1/10000 to <1/1000), very rare (<1/10000) and not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
|System Organ Class||Frequency|
|Blood and lymphatic system disorders
Thrombocytopenia, agranulocytosis, aplastic anemia
|Immune system disorders
|Nervous System Disorders
|Ear and Labyrinth Disorders
Arterial thrombosis, hypertension, hypotension
|Respiratory, Thoracic and Mediastinal Disorders
Asthma, aggravated asthma, bronchospasm, dyspnea
Abdominal pain, nausea, flatulence
Peptic ulcer, gastrointestinal haemorrhage, vomiting, malaena, gastritis
Gastrointestinal perforation, constipation, haematemesis, ulcerative stomatitis, colitis aggravated, Crohn’s Disease aggravated
Liver injury, hepatitis, jaundice
|Skin and subcutaneous tissue disorders
Skin disorder, rash
Angioedema, purpura, pruritus, urticarial
Bullous reaction, erythema multiforme, exfoliative dermatitis, Stevens Johnson Syndorme, toxic epidermal necrolysis
Photosensitivity reaction, skin reaction aggravated
|Renal and urinary disorders
Acute renal failure, interstitial nephritis, papillary necrosis
|General disorders and administration site conditions
Liver function test abnormal
Renal function test abnormal
Central nervous system
Headache, confusion, tinnitus and somnolence have a minor incidence with respect to gastrointestinal effects. Cases of psychotic reaction and depression have been reported. Isolated case on the use of ibuprofen was followed by the onset of severe headache, nausea, vomiting, fever, rigidity of the neck muscles and sensorium obnubilation (initial signs of meningitis).
Reversible effects on the eyes such as toxic amblyopia, blurred vision, color blindness were observed.
Skin and hypersensitivity reactions
Generalized hypersensitivity reactions are only seldom reported. The symptoms may include fever associated with rash, abdominal pain, headache, nausea and vomiting, signs of hepatic dysfunction together with meningism and anapophylactic phenomena.
Systemic lupus erythematosus or other collagen diseases represent risk factors for serious forms of generalized hypersensitivity.
Seldom does ibuprofen induce bronchospasm in predisposed patients.
Daily doses exceeding 1 g of ibuprofen may prolong the bleeding time. Alterations of various nature and intensity affecting the blood profile such as thrombocytopenia, granulocytopenia, agranulocytosis, haemolytic and aplastic anemia were reported. These blood dyscrasias occur particularly after prolonged administration at high doses.
Cases of liver function alterations (high serum transaminases) and jaundice were reported. Hepatotoxicity can occur in cases of generalized hypersensitivity reactions.
Cases of sodium and liquid retention or edema are known. Cases of dysuria were also reported. Kidney failure of various degree of severity could occur, particularly after prolonged administration of high doses.
Acute kidney failure may occur in case of generalized hypersensitivity reactions. Renal damages (papilla necrosis) were also reported.
Occasionally, stomatitis, menstrual irregularities, increase in serum urate levels were reported. The onset of adverse events during treatment implies the immediate suspension of therapy and the attending physician must be notified and consulted immediately.
In general, overdose symptoms include nausea, gastralgia, vomiting (blood) and diarrhea (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.
Management of overdose
There is no specific antidote for ibuprofen. In case of overdosage, the stomach should be emptied as soon as possible. If possible, the patient should vomit. If the patient is unconscious, gastrolavage and correction of severe electrolyte abnormalities are indicated. No specific antidote for ibuprofen is available.
Food, Drugs, Devices and Cosmetics Act prohibits dispensing without prescription.
Store at temperatures not exceeding 25°C.
Ibuprofen arginine (FASPIC) film – coated tablet, 400 mg are supplied in Alu-alu strip x 6’s (box of 30’s).
KEEP OUT OF REACH OF CHILDREN
DO NOT USE BEYOND THE EXPIRY DATE
Via della Chimica, 9
Imported and Distributed by
The Cathay Drug Co., Inc.
2/F Vernida I Condominium
120 Amorsolo St., Legaspi Village Makati City