KETESSE Dexketoprofen Trometamol 25mg Film-Coated Tablet 1's

Ketesse FC tab: Treatment of pain of mild to moderate intensity, like musculo-skeletal, dysmenorrheal, dental pain.
Ketesse Solution for Injection or Concentrate for Solution for Infusion (I.V./I.M.): Symptomatic treatment of acute pain of moderate to severe intensity, when oral administration is not appropriate such as post-operative pain, renal colic and low back pain.

Ketesse FC tab: General Population: According to the nature and severity of pain, the recommended dosage is generally 12.5 mg every 4-6 hours or 25 mg every 8 hours. The total daily dose should not exceed 75 mg. Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.
Dexketoprofen (KETESSE) tablets are not intended for long-term use and the treatment must be limited to the symptomatic period.
Concomitant administration with food delays the absorption rate of the drug (see Pharmacology: Pharmacokinetics under Actions), thus in case of acute pain, it is recommended that administration is at least 30 min before meals.
Elderly: In elderly patients it is recommended to start the therapy at the lower end of the dosage range (50 mg total daily dose). The dosage may be increased to that recommended for the general population only after good general tolerance has been ascertained.
Hepatic Dysfunction: Patients with mild to moderate hepatic dysfunction should start therapy at reduced doses (50 mg total daily dose) and be closely monitored. Dexketoprofen (KETESSE) tablets should not be used in patients with severe hepatic dysfunction.
Renal Dysfunction: The initial dosage should be reduced to 50 mg total daily dose in patients with mildly impaired renal function. Dexketoprofen (KETESSE) tablets should not be used in patients with moderate to severe renal dysfunction (see Contraindications).
Children and adolescents: Dexketoprofen (KETESSE) tablets has not been studied in children and adolescent. Therefore, safety and efficacy have not been established and the product should not be used in children and adolescent.
Ketesse Solution for Injection or Concentrate for Solution for Infusion (I.V./I.M.): Adults: The recommended dose is 50 mg every 8-12 hours. If necessary, the administration can be repeated 6 hours apart. The total daily dose should not exceed 150 mg.
Dexketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion is intended for short term use and the treatment must be limited to the acute symptomatic period (no more than two days). Patients should be switched to an oral analgesic treatment when possible.
Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.
In case of moderate to severe postoperative pain, Dexketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion can be used in combination with opioid analgesics, if indicated, at the same recommended doses in adults.
Elderly: No dosage adjustment is generally necessary in elderly patients. However because of the physiological decline in renal function in elderly patients a lower dose is recommended in case of mild renal function impairment: 50 mg total daily dose.
Liver Disease: The dosage should be reduced to 50 mg total daily dose in patients with mild to moderate (Child-Pugh score 5 - 9) hepatic impairment and hepatic function should be closely monitored. Dexketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion should not be used in patients with severe hepatic dysfunction (Child-Pugh score 10 - 15).
Renal dysfunction: The dosage should be reduced to 50 mg total daily dose in patients with mildly impaired renal function (creatinine clearance 50 - 80 mL/min). Dexketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion should not be used in patients with moderate to severe renal dysfunction (creatinine clearance <50 mL/min).
Dexketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion should not be used in patients with moderate to severe renal dysfunction (creatinine clearance <50 mL/min).
Children and adolescents: Dexketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion has not been studied in children and adolescents. Therefore, safety and efficacy have not been established and the product should not be used in children and adolescents.
Administration: Ketesse Solution for Injection or Concentrate for Solution for Infusion (I.V./I.M.): Dexketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion can be administered either by intramuscular or by intravenous route: Intramuscular use: The content of one ampoule (2 mL) of Dexketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion should be administered by slow Injection deep into the muscle.
Intravenous use: Intravenous infusion: the diluted solution, should be administered as a slow intravenous infusion, lasting 10 to 30 min. The solution must be always protected from natural daylight.
Intravenous bolus: if necessary, the content of one ampoule (2 mL) of Dexketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion can be administered in a slow intravenous bolus over no less than 15 seconds.
Instructions on handling the product: When Dexketoprofen (KETESSE) is administered intramuscularly or as intravenous bolus, the solution should be injected immediately after its removal from the coloured ampoule. For administration as intravenous infusion, the solution should be diluted aseptically and protected from natural daylight.

Should be taken on an empty stomach: Take 30 min before meals, especially for quick relief of acute pain.

Absolute Contraindications: Not to be given to those patients who have history of: Stroke: cerebrovascular accident, CVA.
Heart attack: Myocardial infarction, MI.
Coronary artery bypass graft: CABG.
Uncontrolled hypertension.
Congestive heart failure (CHF) NYHA II-IV.
Ketesse FC tab: Dexketoprofen (KETESSE) tablets must not be administered in the following cases: patients hypersensitive to Dexketoprofen, to any other NSAID, or to any of the excipients of the product; patients in whom substances with a similar action (e.g. aspirin, or other NSAIDs) precipitate attacks of asthma, bronchospasm, acute rhinitis, or cause nasal polyps, urticaria or angioneurotic edema; patients with active or suspected peptic ulcer/haemorrhage or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding) or chronic dyspepsia; patients with history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy; patients who have gastrointestinal bleeding or other active bleedings or bleeding disorders; patients with Crohn's disease or ulcerative colitis; patients with a history of bronchial asthma; patients with severe heart failure; patients with moderate to severe renal dysfunction; patients with severely impaired hepatic function; patients with haemorrhagic diathesis and other coagulation disorders; during the third trimester of pregnancy and the lactation period.
Ketesse Solution for Injection or Concentrate for Solution for Infusion (I.V/I.M.): Dexketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion must not be administered in the following cases: patients hypersensitive to Dexketoprofen, to any other NSAID, or to any of the excipients of this medicinal product; patients in whom substances with a similar action (e.g. acetylsalicylic acid and other NSAIDs) precipitate attacks of asthma, bronchospasm, acute rhinitis, or cause nasal polyps, urticaria or angioneurotic edema; patients with active or suspected peptic ulcer/haemorrhage or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding); patients who have gastrointestinal bleeding or other active bleedings or bleeding disorders; patients with history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy; patients with Crohn's disease or ulcerative colitis; patients with a history of bronchial asthma; patients with severe heart failure; patients with moderate to severe renal dysfunction (creatinine clearance <50 mL/min); patients with severely impaired hepatic function (Child-Pugh score 10-15); patients with haemorrhagic diathesis and other coagulation disorders; during the third trimester of pregnancy and the lactation period.
Decketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion is contraindicated for neuraxial (intrathecal or epidural) administration due to its ethanol content.

Ketesse FC tab: The safe use in children and adolescents has not been established.
Administer with caution in patients with a history of allergic conditions.
The use of Dexketoprofen (KETESSE) with concomitant other NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.
Undesirable effects may be minimized by using the minimum effective dose for the shortest duration necessary to control symptoms.
Gastrointestinal bleeding, ulceration or perforation which can be fatal, have been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. When gastrointestinal bleeding or ulceration occurs in patients receiving Dexketoprofen (KETESSE), the treatment should be withdrawn.
The risk of gastrointestinal 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.
As with all NSAIDs, any history of esophagitis, gastritis and/or peptic ulcer must be sought in order to ensure their total cure before starting treatment with Dexketoprofen trometamol. Patients with gastrointestinal symptoms or history of gastrointestinal disease should be monitored for digestive disturbances, especially gastrointestinal bleeding.
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.
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 toxicity, 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.
All non-selective NSAIDs can inhibit platelet aggregation and prolong bleeding time via inhibition of prostaglandin synthesis. Therefore, the use of Dexketoprofen trometamol in patients who are receiving other therapy that interferes with haemostasis, such as warfarin or other coumarins or heparins is not recommended.
As with all NSAIDs, it can increase plasma urea nitrogen and creatinine. As with other inhibitors of prostaglandin synthesis, it can be associated with adverse effects on the renal system which can lead to glomerular nephritis, interstitial nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure.
As with other NSAIDs, it can cause transient small increases in some liver parameters, and also significant increases in SGOT and SGPT. In case of a relevant increase in such parameters, therapy must be discontinued.
Dexketoprofen (KETESSE) tablets should be administered with caution to patients suffering from haematopoietic disorders, systemic lupus erythematosus or mixed connective tissue disease. As other NSAIDs, Dexketoprofen can mask the symptoms of infectious diseases.
Caution should be exercised in patients with impairment of hepatic and/or renal functions as well as in patients with a history of hypertension and/or heart failure. In these patients, the use of NSAIDs may result in deterioration of renal function, fluid retention and edema. Caution is also required in patients receiving diuretic therapy or those who could develop hypovolaemia as there is an increased risk of nephrotoxicity. Special caution should be exercised in patients with a history of cardiac disease, in particular those with previous episodes of heart failure as there is an increased risk of triggering heart failure.
Elderly patients are more likely to be suffering from impaired renal cardiovascular or hepatic function.
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. 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. Dexketoprofen (KETESSE) should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
As with other NSAIDs, the use of Dexketoprofen trometamol 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 Dexketoprofen trometamol should be considered. 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 edema have been reported in association with NSAIDs therapy.
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for Dexketoprofen trometamol.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with Dexketoprofen trometamol after careful consideration. Similar consideration should be made before initiating longer-term treatment of the patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Ketesse Solution for Injection or Concentrate for Solution for Infusion (I.V./I.M.): The safe use in children and adolescents has not been established.
Administer with caution in patients with a history of allergic conditions.
The use of Dexketoprofen (KETESSE) with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.
Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.
Gastrointestinal bleeding, ulceration and perforation: gastrointestinal 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 gastrointestinal events. When gastrointestinal bleeding or ulceration occurs in patients receiving dexketoprofen, the treatment should be withdrawn.
The risk of gastrointestinal 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.
NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn’s disease) as these condition may be exacerbated.
As with all NSAIDs, any history of oesophagitis, gastritis and/or peptic ulcer must be sought in order to ensure their total cure before starting treatment with Dexketoprofen trometamol. Patients with gastrointestinal symptoms or history of gastrointestinal disease should be monitored for digestive disturbances, especially gastrointestinal bleeding.
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 toxicity, 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.
All non-selective NSAIDs can inhibit platelet aggregation and prolong bleeding time via inhibition of prostaglandin synthesis. The concomitant use of dexketoprofen trometamol and prophylactic doses of low molecular weight heparin in the postoperative period has been assessed in controlled clinical trials and no effect on coagulation parameters was observed. Nevertheless, patients who are receiving therapy that interferes with haemostasis, such as warfarin or other coumarins or heparins should be carefully monitored if dexketoprofen trometamol is administered.
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/or edema have been reported in association with NSAID therapy.
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for Dexketoprofen Trometamol.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with Dexketoprofen Trometamol after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
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. 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. Dexketoprofen (KETESSE) should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
As with all NSAIDs, it can increase plasma urea nitrogen and creatinine. As with other inhibitors of prostaglandin synthesis, it can be associated with adverse effects on the renal system, which can lead to glomerular nephritis, interstitial nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure.
As with other NSAIDs, it can cause transient small increases in some liver parameters, and also significant increases in SGOT and SGPT. In case of a relevant increase in such parameters, therapy must be discontinued.
Caution should be exercised in patients with impairment of hepatic and/or renal functions as well as in patients with a history of hypertension and/or heart failure. In these patients, the use of NSAIDs may result in deterioration of renal function, fluid retention and edema.
Caution is also required in patients receiving diuretic therapy or those who could develop hypovolaemia as there is an increased risk of nephrotoxicity. Special caution should be exercised in patients with a history of cardiac disease, in particular those with previous episodes of heart failure as there is an increased risk of triggering heart failure.
Elderly patients are more likely to be suffering from impaired renal cardiovascular or hepatic function.
Dexketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion should be administered with caution to patients suffering from haematopoietic disorders, systemic lupus erythematosus or mixed connective tissue disease.
As other NSAIDs, dexketoprofen can mask the symptoms of infectious diseases. In isolated cases an aggravation of soft tissue infections has been described in temporal connection with the use of NSAIDs. Therefore the patient is advised to consult a physician immediately if signs of a bacterial infection occur or worsen during therapy.
As with other NSAIDs, the use of dexketoprofen trometamol 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 dexketoprofen trometamol should be considered. Dexketoprofen should not be used during first and second trimester of pregnancy unless clearly necessary.
Each ampoule of Dexketoprofen (KETESSE) Solution for Injection or concentrate for solution for infusion contains 200 mg of ethanol equivalent to 5 mL beer or 2.08 mL wine per dose.
Harmful for those suffering from alcoholism.
To be taken into account in pregnant and breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially "sodium-free".
Effects on the ability to drive and use machines: Ketesse FC tab and Ketesse for Solution for Injection or Concentrate for Solution for Infusion (I.V./I.M.): Dexketoprofen (KETESSE) tablets can cause minor or moderate effects/influence on the ability to drive or use machines due to the possibility of dizziness or drowsiness occurring.
Use in elderly: The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
These patients should commence treatment on the lowest dose available.

The adverse reactions reported as at least possibly related with dexketoprofen trometamol in clinical trials, as well the adverse reactions reported after the marketing of Ketesse tablets and solution for injection or concentrate for solution for infusion are tabulated as follows, classified by system organ class and ordered by frequency: (See Table 1 and Table 2.)

 

 

Gastrointestinal: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal 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 administration. Less frequently, gastritis has been observed. Edema, hypertension and cardiac failure have been reported in association with NSAIDs treatment.
As with other NSAIDs the following undesirable effects may appear: Aseptic meningitis, which might predominantly occur in patients with systemic lupus erythematosus or mixed connective tissue disease; hematological reactions (purpura, aplastic and hemolytic anemia and rarely agranulocytosis and medullar hypoplasia).
Bullous reactions including Stevens-Johnson syndrome and Toxic Epidermal Necrolysis (very rare).
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long-term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).

The following interactions apply to non-steroidal anti-inflammatory drugs (NSAIDs) in general: Inadvisable combinations: Other NSAIDs, including high doses of salicylates ≥3 g/day): administration of several NSAIDs together may increase the risk of gastrointestinal ulcers and bleeding, via a synergistic effect.
Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin, due to the high plasma protein binding of Dexketoprofen and the inhibition of platelet function and damage to the gastroduodenal mucosa. If the combination cannot be avoided, close clinical observation and monitoring of laboratory values should be carried out.
Corticosteroids: There is an increased risk of gastrointestinal ulceration or bleeding.
Lithium (described with several NSAIDs): NSAIDs increase blood lithium levels, which may reach toxic values (decreased renal excretion of lithium). This parameter therefore requires monitoring during the initiation, adjustment and withdrawal of treatment with dexketoprofen.
Methotrexate, used at high doses of 15 mg/week or more: increased haematological toxicity of methotrexate via a decrease in its renal clearance by antiinflammatory agents in general.
Hydantoines and sulphonamides: the toxic effects of these substances may be increased.
Ketesse FC tab: Heparins: increased risk of haemorrhage (due to the inhibition of platelet function and damage to the gastroduodenal mucosa). If the combination cannot be avoided, close clinical observation and monitoring of laboratory values should be carried out.
Combinations requiring precautions: Diuretics, ACE inhibitors and angiotensin II receptor antagonists: Dexketoprofen may reduce the effect of diuretics and other antihypertensive drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the co-administration of agents that inhibit cyclo-oxygenase and ACE inhibitors or angiotensin II receptor antagonists may result in further deterioration of renal function, which is usually reversible. In case of combined prescription of Dexketoprofen and a diuretic, it is essential to ensure that the patient is adequately hydrated and to monitor renal function at the start of the treatment.
Methotrexate, used at low doses, less than 15 mg/week: increased haematological toxicity of methotrexate via a decrease in its renal clearance by antiinflammatory agents in general. Weekly monitoring of blood count during the first weeks of the combination. Increased surveillance in the presence of even mildly impaired renal function, as well as in the elderly.
Pentoxyfylline: increased risk of bleeding. Intensify clinical monitoring and check bleeding time more often.
Zidovudine: risk of increased red cell line toxicity via action on reticulocytes, with severe anaemia occurring one week after the NSAID is started. Check complete blood count and reticulocyte count one to two weeks after starting treatment with the NSAID.
Sulfonylureas: NSAIDs can increase the hypoglycaemic effect of sulfonylureas by displacement from plasma protein binding sites.
Combinations needing to be taken into account: Beta-blockers: treatment with a NSAID may decrease their antihypertensive effect via inhibition of prostaglandin synthesis.
Cyclosporin and tacrolimus: nephrotoxicity may be enhanced by NSAIDs via renal prostaglandin mediated effects. During combination therapy, renal function has to be measured.
Thrombolytics: increased risk of bleeding.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.
Probenecid: plasma concentrations of dexketoprofen may be increased; this interaction can be due to an inhibitory mechanism at the site of renal tubular secretion and of glucuronoconjugation and requires adjustment of the dose of dexketoprofen.
Cardiac glycosides: NSAIDs may increase plasma glycoside concentration.
Mifepristone: Because of a theoretical risk that prostaglandin synthetase inhibitors may alter the efficacy of mifepristone, NSAIDs should not be used for 8-12 days after mifepristone administration.
Quinolone: Animal data indicate that high doses of quinolones in combination with NSAIDs can increase the risk of developing convulsions.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)