Active ingredients: Ketoprofen
Ardbeg 80mg Adult - Powder for oral solution
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
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01.0 NAME OF THE MEDICINAL PRODUCT
ARDBEG 80 MG ADULT POWDER FOR ORAL SOLUTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One sachet contains:
active principle: ketoprofen lysine salt 80 mg (equivalent to 50 mg of ketoprofen).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Powder for oral solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Adults: symptomatic treatment of inflammatory states associated with pain, including: rheumatoid arthritis, ankylosing spondylitis, painful arthrosis, extra-articular rheumatism, post-traumatic inflammation, painful inflammatory diseases in dentistry, otolaryngology, urology and pneumology.
04.2 Posology and method of administration
Adults: one 80 mg sachet (full dose) three times a day with meals.
Senior citizens: the dosage must be carefully established by the doctor who will have to evaluate a "possible reduction of the dosages indicated above (see section 4.4).
Patients with hepatic insufficiency: it is recommended to start therapy at the minimum daily dosage (see section 4.4).
Patients with mild or moderate renal insufficiency: it is advisable to monitor the volume of diuresis and renal function (see section 4.4).
Instructions: Pour the contents of one sachet into half a glass of water and mix.
04.3 Contraindications
Ketoprofen lysine salt should not be administered in the following cases:
- manifest hypersensitivity to the active substance, to other non-steroidal anti-inflammatory drugs (NSAIDs) or to any of the excipients;
- patients in whom substances with a similar mechanism of action (for example acetylsalicylic acid or other NSAIDs) cause asthma attacks, bronchospasm, acute rhinitis, or cause nasal polyps, urticaria or angioneurotic edema;
- active peptic ulcer, or a history of gastrointestinal bleeding, ulceration or perforation or chronic dyspepsia;
- gastrointestinal bleeding or other active bleeding or bleeding disorders
- Crohn's disease or ulcerative colitis;
- previous bronchial asthma;
- severe heart failure;
- severe liver or kidney dysfunction;
- bleeding diathesis and other coagulation disorders, or patients subject to anticoagulant therapy
- pregnancy and lactation (see section 4.6);
- children and adolescents under the age of 14.
04.4 Special warnings and appropriate precautions for use
Concomitant use of Ardbeg with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided (see section 4.5).
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
Administer with caution in patients with allergic manifestations or previous allergy.
Treatment with ketoprofen lysine salt should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Patients with current or previous gastrointestinal disease should be carefully monitored for the appearance of digestive disorders, especially gastrointestinal bleeding. In some pediatric patients treated with ketoprofen lysine salt, gastrointestinal haemorrhages, occasionally severe, and ulcer have been reported (see section 4.8); therefore the product must be administered under strict supervision of the physician who will have to evaluate the necessary dosage schedule each time.
As with all NSAIDs, the drug can increase plasma urea nitrogen and creatinine.
As with other prostaglandin synthesis inhibitors, the drug may be associated with adverse events on the renal system which can lead to glomerular nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure.
As with other NSAIDs, the drug can cause small transient increases in some liver parameters and also significant increases in SGOT and SGPT (see section 4.8). In the event of a significant increase in these parameters, therapy must be discontinued.
Ketoprofen lysine salt should be administered with caution in patients with haematopoietic disorders, systemic lupus erythematosus or mixed connective tissue disorders.
As with other NSAIDs, ketoprofen lysine salt can mask the symptoms of infectious diseases.
Caution should be exercised in the event of impaired hepatic, renal (see section 4.2) or cardiac function as well as in the presence of other conditions predisposing to fluid retention. In these cases, the use of NSAIDs can cause deterioration of kidney function and fluid retention.Caution is also required in patients undergoing diuretic therapy or who are likely to be hypovolaemic because the risk of nephrotoxicity is increased.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in conjunction with the use of NSAIDs (see section 4.8). In the early stages of therapy, patients appear to be be at higher risk: the onset of the reaction occurs in most cases within the first month of treatment.
Elderly patients are more prone to decreased renal, cardiovascular or hepatic function. Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2). Gastrointestinal bleeding, ulceration and perforation: Gastrointestinal bleeding, ulceration and perforation, which can be fatal, have been reported during treatment with all NSAIDs, at any time, with or without warning symptoms or a previous history of serious gastrointestinal events. Some epidemiological evidence suggests that ketoprofen may be associated with a higher risk of severe gastrointestinal toxicity than other NSAIDs, especially at high doses (see also sections 4.2 and 4.3). In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing doses of NSAIDs. These patients should start treatment with the lowest available dose and should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment. Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low dose aspirin or other drugs that may increase the risk of gastrointestinal events (see below and section 4.5).
Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any abdominal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.
Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as aspirin (see section 4.5).
When gastrointestinal bleeding or ulceration occurs in patients taking Ardbeg the treatment should be discontinued. NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8 Undesirable effects).
The use of ketoprofen lysine salt, as well as any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended for women intending to become pregnant.
The administration of ketoprofen lysine salt should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
Adequate monitoring and instruction are required in patients with a history of mild to moderate hypertension and / or congestive heart failure as fluid retention and edema have been reported in association with NSAID treatment.
Patients with established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with ketoprofen lysine salt after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (eg hypertension, hyperlipidaemia, diabetes mellitus, smoking).
04.5 Interactions with other medicinal products and other forms of interaction
The following interactions relate to NSAIDs in general:
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Anticoagulants: NSAIDs may amplify the effects of anticoagulants, such as warfarin (see section 4.4).
Anti-aggregating agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).
Associations not recommended:
• Other NSAIDs, including high doses of salicylates (≥ 3 g / day): the simultaneous administration of several NSAIDs may increase the risk of gastrointestinal ulcers and bleeding, due to a synergistic effect.
• Oral anticoagulants, parenteral heparin and ticlopidine: increased risk of bleeding due to inhibition of platelet function and damage to the gastrointestinal mucosa.
• Lithium (described with several NSAIDs): NSAIDs increase plasma lithium levels (decreased renal excretion of lithium), which can reach toxic values. This parameter therefore needs to be monitored during initiation, dose adjustment and after discontinuation of ketoprofen lysine salt treatment.
• Methotrexate, used at high doses of 15 mg / week or more: increased blood toxicity of methotrexate due to a decrease in its renal clearance due to anti-inflammatory agents in general.
• Hydantoins and sulfonamides: the toxic effects of these substances can be increased.
Associations requiring precaution:
• Diuretics, ACE inhibitors and angiotensin II antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (eg dehydrated patients or elderly patients with impaired renal function) the co-administration of an ACE inhibitor or antagonist angiotensin II and agents that inhibit the cyclo-oxygenase system may lead to further deterioration of renal function, including possible acute renal failure, usually reversible. These interactions should be considered in patients taking ketoprofen lysine salt concomitantly with ACE inhibitors or angiotensin 11 antagonists. Therefore, the combination should be administered with caution, especially in elderly patients. Patients should be adequately hydrated and should be Consideration of monitoring of renal function after initiation of concomitant therapy.
• Methotrexate, used at low doses, less than 15 mg / week: increased blood toxicity of methotrexate due to a decrease in its renal clearance due to anti-inflammatory agents in general. Perform weekly monitoring of the blood count during the first weeks of the association. Increase monitoring in the presence of even mild worsening of renal function, as well as in the elderly.
• Pentoxifylline: increased risk of bleeding. Increase clinical monitoring and check bleeding time more frequently.
• Zidovudine: risk of increased toxicity on the red cell line by action on reticulocytes, with severe anemia occurring one week after starting treatment with the NSAID. Check the complete blood count and reticulocyte count one or two weeks after having started treatment with the NSAID.
• Sulfonylureas: NSAIDs can increase the hypoglycemic effect of sulfonylureas by displacing them from binding sites with plasma proteins.
Associations that need to be considered:
• Beta blockers: treatment with an NSAID may decrease their antihypertensive effect by inhibiting the synthesis of prostaglandins.
• Ciclosporin and tacrolimus: Nephrotoxicity can be increased by NSAIDs due to effects mediated by renal prostaglandins. Renal function should be measured during associated therapy.
• Thrombolytics: increased risk of bleeding.
• Probenecid: plasma concentrations of ketoprofen lysine salt may be increased; this interaction may be due to an inhibitory mechanism at the site of renal tubular secretion and glucuronide conjugation and requires dose adjustment of the ketoprofen lysine salt.
04.6 Pregnancy and lactation
Use in pregnancy
Inhibition of prostaglandin synthesis may adversely affect pregnancy and / or embryolfactory development; therefore, ketoprofen lysine salt should not be administered during pregnancy.
Results of epidemiological studies suggest an increased risk of abortion and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately I "1.5%. The risk has been considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased loss of pre- and post-implantation and of embryo-fetal mortality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to
• cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
• renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
the mother and the newborn, at the end of pregnancy, to:
• possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;
• inhibition of uterine contractions resulting in delayed or prolonged labor.
Use while sleeping
Ketoprofen lysine salt should not be administered during breastfeeding.
04.7 Effects on ability to drive and use machines
The drug has a small or moderate influence on the ability to drive or use machines, due to the possible onset of dizziness or somnolence (see section 4.8).
04.8 Undesirable effects
The experience derived from the marketing of oral formulations of ketoprofen salt of lysine shows that the occurrence of undesirable effects is a very rare event. Based on the estimate of exposed patients, derived from the number of packs sold, and considering the number of spontaneous reports, less one out of every 100,000 patients experienced adverse reactions, in most cases the symptoms were transient and resolved upon discontinuation of therapy and, in some cases, with specific pharmacological treatment.
Adverse reactions seen with oral formulations of ketoprofen lysine salt, all very rare (incidence
• Skin and appendages: urticaria, erythema, rash, maculo-papular rash, pruritus, angioedema, dermatitis, rash, skin rash.
• Gastrointestinal disorders: The most commonly observed adverse events are gastrointestinal in nature. Gastric and abdominal pain, nausea, vomiting, diarrhea, dyspepsia, heartburn, flatulence and constipation, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of Ardbeg (see section 4.4). Occasionally severe gastrointestinal bleeding and peptic, gastric and duodenal ulcer, gastritis and erosive gastritis, with gastrointestinal perforation and / or haemorrhage sometimes fatal, particularly in the elderly, may occur (see section 4.4). Two single cases of ulcerative stomatitis and tongue edema have been reported, respectively. Elevations of liver enzymes and hepatitis have been reported. Gastritis has been observed less frequently.
• General conditions: allergic and anaphylactoid reactions, anaphylactic shock, edema of the mouth. Single cases of peripheral edema and syncope have been reported, respectively.
• Nervous system: dizziness and vertigo. A single case of tremor and hyperkinesis has been reported in an elderly patient treated concomitantly with a quinolone antibiotic.
• Cardiovascular system: palpitations, tachycardia, hypotension, hypertension, edema, heart failure. Cases of vasculitis and skin redness have been exceptionally reported. The use of some NSAIDs (especially at high doses and for long-term treatments) may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke)
• Respiratory System: bronchospasm, dyspnoea, laryngeal edema and laryngospasm. A single case of acute respiratory failure with fatal outcome has been reported in an aspirin-sensitive asthmatic patient.
• Disorders of the blood crasis: Single cases of leukocytosis, lymphangitis, purpura, thrombocytopenic purpura, thrombocytopenia and leukocytopenia have been reported respectively.
• Disorders of the urinary tract: face edema and hematuria. A single case of oliguria has been reported.
• Metabolic disorders: periorbital edema.
A single case of anxiety, visual hallucinations, hyperexcitability and altered behavior was reported in a pediatric patient who received twice the dose recommended in the CPR. Symptoms disappeared spontaneously within 1-2 days. Adverse reactions that were severe in nature, all very rare, mainly included cases of skin reactions (urticaria, erythema, rash, angioedema), gastrointestinal and burdensome reactions. respiratory tract (bronchospasm, dyspnoea, laryngeal edema), as well as episodic cases of allergic / anaphylactoid reactions, anaphylactic shock and mouth edema. As already mentioned, a single case of acute respiratory failure, which occurred in an asthmatic and sensitive patient "aspirin, had a fatal outcome. Most of the reactions occurring in allergic / asthmatic patients and / or with known hypersensitivity to NSAIDs were of a serious nature.
Some undesirable effects have been observed only occasionally following the administration of ketoprofen: constipation, paraesthesia, excitability, insomnia, chills, transient dyskinesia, asthenia, headache; photosensitivity reactions.
Some NSAIDs, including ketoprofen lysine salt, can cause, but are extremely rare, severe mucocutaneous reactions (bullous reactions including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis, Lyell) and haematological reactions (aplastic and haemolytic anemia, and rarely agranulocytosis and hypoplasia medullary).
04.9 Overdose
There are no known cases of overdose. In case of overdose with evident clinical manifestations, immediately institute symptomatic therapy and apply the usual emergency measures (gastric lavage, activated charcoal meal, parenteral administration of liquid, etc.), if necessary.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-inflammatory, antirheumatic, non-steroidal drugs. Derivatives of propionic acid. ATC: MO1AE03
Ketoprofen lysine salt is the lysine salt of 2- (3-benzoylphenyl) propionic acid, an analgesic, anti-inflammatory and antipyretic drug belonging to the class of NSAIDs (M01AE). Ketoprofen lysine salt is more soluble than acid ketoprofen.
The mechanism of action of NSAIDs is related to the reduction of prostaglandin synthesis by inhibiting the cyclooxygenase enzyme.
Specifically, there is an inhibition of the transformation of arachidonic acid into cyclic endoperoxides, PGG 2 and PGH 2, precursors of prostaglandins PGE 1, PGE 2, PGF 2a and PGD 2 and also of prostacyclin PGI 2 and thromboxanes (TxA 2 and TxB 2). Furthermore, the inhibition of prostaglandin synthesis can interfere with other mediators such as kinins, causing an indirect action that would add to the direct action.
Ketoprofen lysine salt possesses a marked analgesic effect, correlated both with its anti-inflammatory effect and with a central effect.
Ketoprofen lysine salt exerts an antipyretic activity without interfering with the normal thermoregulation processes.
Painful inflammatory manifestations are eliminated or attenuated by promoting joint mobility.
05.2 "Pharmacokinetic properties
The ketoprofen lysine salt possesses higher solubility than acid ketoprofen.
The form for oral use allows the assumption of the active principle already in aqueous solution and therefore leads to a rapid increase in plasma levels and an early reaching of the peak value. This is manifested, clinically, with a more rapid onset and a greater intensity of the analgesic and anti-inflammatory effect.
The kinetic profile in the child does not differ from that of the adult.
Repeated administration does not change the kinetics of the drug or produce accumulation.
Ketoprofen is 95-99% bound to plasma proteins. Significant levels of ketoprofen were found in tonsillar tissue and synovial fluid after systemic administration.
Elimination is rapid and essentially via the kidney: 50% of the product administered systemically is excreted in the urine in 6 hours. Ketoprofen is extensively metabolised: about 60-80% of the product administered systemically is in the form of metabolites in the urine.
05.3 Preclinical safety data
The LD 50 of ketoprofen lysine salt in rats and mice orally resulted respectively of 102 and 444 mg / kg, equal to 30-120 times the active dose as anti-inflammatory and analgesic in the animal.Intraperitoneally, the LD 50 of ketoprofen lysine salt was 104 and 610 mg / kg respectively in rats and mice.
Prolonged treatment in rats, dogs and monkeys with oral ketoprofen lysine salt at doses equal to or higher than the prescribed therapeutic dosages did not cause the appearance of any toxic phenomenon. At high doses, gastrointestinal and renal alterations were found due to the known side effects caused in animals by non-steroidal anti-inflammatory drugs. In a prolonged toxicity study conducted in rabbits by the oral or rectal route, ketoprofen was shown to be better tolerated when administered orally. rectal versus oral In an intramuscular tolerability study in rabbits, ketoprofen lysine salt was well tolerated.
Ketoprofen lysine salt was found to be non-mutagenic in genotoxicity tests carried out "in vitro" and in "vivo". Carcinogenicity studies with ketoprofen in mice and rats showed the absence of carcinogenic effects.
As regards embryo-fetal toxicity and teratogenesis of NSAIDs in animals, see section 4.6.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Sorbitol, anhydrous colloidal silica, sodium chloride, sodium saccharin, mint flavor.
06.2 Incompatibility
Not known.
06.3 Period of validity
24 months
06.4 Special precautions for storage
Do not store above 30 ° C.
06.5 Nature of the immediate packaging and contents of the package
Lithographed cardboard box containing 30 paper / aluminum / polythene sachets.
06.6 Instructions for use and handling
No special instructions.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
S.F. Group S.r.l. Via Beniamino Segre, 59 - 00134 Rome
08.0 MARKETING AUTHORIZATION NUMBER
ARDBEG 80 mg ADULTS powder for oral solution - 30 sachets AIC: 039413012
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
February 8, 2011
10.0 DATE OF REVISION OF THE TEXT
AlFA determination date: 23 April 2012
