ENANTYUM BUSTINE 25 mg

 

Anti-inflammatory drug useful for the treatment of pain of different origin mild to moderate intensity like headache, toothache, joint pains.

 

Indications

Symptomatic treatment of short duration of painful affections of intensity ‘mild to moderate, such as acute muscle-skeletal pain, dysmenorrhoea and dental pain.

 

Contraindications
Hypersensitivity ‘ascertained to dexketoprofen, or to any other NSAID, or to any of the excipients; patients who developed asthma, bronchospasm, acute rhinitis, nasal polyps or urticaria angioneurotic edema after exposure to substances from similar mechanism of action (eg. aspirin, or other NSAIDs); Patients with known phototoxic or photoallergic reactions during treatment with ketoprofen or -fibrati; Patients with a history of bleeding or gastrointestinal perforation related to previous therapy with NSAIDs; patients with recurrent peptic ulcer / Gastrointestinal hemorrhage in place, or history of recurrent peptic / gastrointestinal bleeding ulcer (two or more ‘distinct episodes of ulceration or bleeding documented); patients with chronic dyspepsia or suspected ulcers / ulcer bleeding; Patients who have other active bleeding or bleeding disorders; Patients with Crohn’s disease or ulcerative colitis; Patients with severe heart failure; Patients with moderate to severe renal insufficiency; Patients with severe hepatic impairment; Patients with bleeding diathesis and other coagulation disorders; Patients with severe dehydration (caused by vomiting, diarrhea or insufficient fluid intake); during the third trimester of pregnancy el ‘lactation.

 

Dosage
Adults: according to the nature and ‘intensity ‘ pain, the recommended dose ‘generally 12.5 mg every 4-6 hours or 25 mg every 8 hours. The total daily dose should not exceed 75 mg. Side effects may be minimized by using the lowest effective dose for the time necessary to eliminate the symptoms. The medication ‘indicated only for short-term treatment and the administration must be limited to the symptomatic period. Concomitant administration of food delays the rate ‘absorption of the drug, so that, in case of acute pain, it is recommended to administer the drug at least 15 minutes before meals. Elderly: in elderly patients is recommended to start treatment with the therapeutic dose more ‘low (50 mg total daily dose). The dosage can ‘be increased in order to achieve that recommended for the ‘ adult only after that will ‘a good tolerability ‘ been established.

Because of the risk profile, the elderly should be monitored carefully. Hepatic dysfunction: Patients with mild to moderate hepatic dysfunction should start therapy at reduced doses (50 mg total daily dose) under strict medical supervision. The drug should not be used in patients with severe hepatic dysfunction. Renal impairment: in patients with mild renal impairment, the initial dosage should be reduced to 50 mg total daily dose. The drug should not be used in patients with moderate to severe renal insufficiency. Children and adolescents: the product is not ‘been studied in children and adolescents. Therefore, there are no available safety and efficacy data, the product should not be used in children and adolescents.

 

Warnings
security is not ‘d been established ‘ use in children and adolescents. Use with caution in patients with a history of allergic conditions. Avoid ‘concurrent use of the drug with other NSAIDs. Side effects may be minimized by using the lowest effective dose for the time necessary to eliminate the symptoms. Bleeding, ulceration or potentially fatal gastrointestinal perforation have been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events, discontinue therapy. The risk of bleeding, ulceration or gastrointestinal perforation increases with ‘Increased doses of NSAIDs in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation and in the elderly. The elderly have an increased frequency of adverse reactions to NSAIDs. Start treatment with the lowest available dose. Before starting treatment, it must investigate past esophagitis, gastritis and / or peptic ulcers and ensure their total cure. Monitor patients with gastrointestinal symptoms or history of gastrointestinal disease. NSAIDs administered with caution to patients with a history of gastrointestinal disease, because ‘these conditions may be exacerbated.

L ‘concurrent use of protective agents should be considered for these patients and for patients receiving concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk. Caution is recommended in patients who are co-administered drugs that may increase the risk of ulcer or bleeding. Use with caution in patients with impaired function ‘kidney. In these patients l ‘use of NSAIDs can ‘ cause deterioration of the function ‘kidney, fluid retention and edema. Caution should be exercised, to an increased risk of nephrotoxicity ‘, even in patients receiving diuretic therapy or at risk of developing hypovolemia. During treatment must be guaranteed ‘adequate fluid intake to prevent dehydration and the risk of toxicity ‘ kidney. The product can ’cause increased ‘ s blood urea and creatinine. You may occur dependent side effects of the kidney that can lead to glomerular nephritis, interstitial nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure. Elderly patients are the most ‘at risk of kidney failure. Caution should be exercised in patients with impaired function ‘liver. Can ’cause transient small increases in some parameters of function ‘ liver, and also significant increases of GOT and GPT. In the case of a relevant increase in such parameters, discontinue therapy. Elderly patients are the most ‘exposed to risk of failure of the function ‘ liver.

For patients with a history of hypertension and / or heart failure mild to moderate and ‘you need to be properly monitored. Caution should be exercised in patients with cardiac disease, especially those with a history of heart failure because ‘c ‘ and ‘increased risk of heart failure, as they have been reported fluid retention and edema in association ‘ s use of NSAIDs. clinical and epidemiological data suggest that the ‘Use of some NSAIDs (particularly high doses and prolonged treatment) can ‘ be associated with a small increased risk of arterial thrombotic events. There are insufficient data to exclude such a risk for dexketoprofen trometamol. Therefore, patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should be treated with dexketoprofen trometamol only after ‘accurate assessment. Pay attention before starting a long-term treatment in patients with risk factors for cardiovascular disease. All non-selective NSAIDs can inhibit l ‘platelet aggregation and prolong bleeding time via inhibition of prostaglandin synthesis. L ‘use of dexketoprofen trometamol not ‘ therefore recommended in patients receiving an ‘other therapy that interferes with l ‘ hemostasis, such as warfarin or other coumarins or heparins. Elderly patients, in general, are the most ‘exposed to the risk of failure of the function ‘ cardiovascular. Severe skin reactions (some of them fatal) have been reported very rarely in association with l ‘use of NSAIDs. In the early stages of therapy the patients seem to piu ‘high risk: l ‘ onset of the reactions occurs, in most cases, within the first month of treatment. At the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity ‘, discontinue therapy.

Particular caution and ‘required in patients with: Congenital abnormalities of porphyrin metabolism; dehydration; immediately after a major surgery. If it sees a need for long-term treatment with dexketoprofen you must regularly check the functionality ‘liver, kidney el ‘ full blood count. Severe hypersensitivity reactions ‘acute were observed in very rare cases. At the first event of serious reactions of hypersensitivity ‘stop treatment. In exceptional cases, chickenpox can ‘be associated with infectious complications of skin and soft tissues. To date can not ‘be excluded a role of NSAIDs in ‘ aggravation of such infections, so it ‘s best to avoid ‘ use of the drug in patients with chickenpox. Administer the medicine with caution to patients suffering from haematopoietic disorders, systemic lupus erythematosus or mixed connective tissue disease. Dexketoprofen can ‘mask the symptoms of infectious diseases. This medicine contains sucrose.

Interactions

The following interactions are characteristic of anti-inflammatory drugs (NSAIDs) in general. >> Combinations not recommended. Other NSAIDs, including high doses of salicylates (> = 3 g / day): co-administration of more ‘NSAIDs can ‘ increase the risk of ulceration and gastrointestinal bleeding due to a synergistic effect. Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin, because of ‘high plasma protein binding of dexketoprofen, ‘ s inhibition of platelet function and damage to the gastro-duodenal mucosa.

If not ‘can avoid the ‘ Association, it requires a rigorous clinical observation and monitoring of laboratory parameters. Heparins: increased risk of haemorrhage (due to ‘inhibition of platelet function and damage to the gastrointestinal mucosa). If not ‘can avoid the ‘ Association, it requires a rigorous clinical observation and monitoring of laboratory parameters. Corticosteroids: increased risk of gastrointestinal ulceration or bleeding. Lithium (described with several NSAIDs): NSAIDs increase blood lithium levels with risk of reach toxic values ​​(decreased renal excretion of lithium). This parameter therefore requires careful monitoring ‘s beginning, during the ‘ adjustment and the end of treatment with dexketoprofen. Methotrexate if used in high doses (> = 15 mg / week): increased toxicity ‘haematological of methotrexate due to a decrease in its renal clearance, in general with NSAIDs. Hydantoins and sulfonamides: the toxic effects of these substances may be increased.

Combinations requiring caution. Diuretics, ACE-inhibitors, aminoglycoside antibiotics and antagonists of the receptor ‘angiotensin II: dexketoprofen can ‘ reduce ‘effect of diuretics and antihypertensive drugs. In some patients with functionality ‘impaired renal (eg dehydrated patients or elderly patients with functionality ‘ impaired renal), the coadministration of agents that inhibit cyclo-oxygenase and ACE inhibitors, angiotensin receptor ‘s angiotensin II or antibiotics aminoglycosides can ’cause a further deterioration of the function ‘ kidney, usually reversible. In the case of co-prescription of dexketoprofen and a diuretic, and ‘essential to ensure adequate hydration of the patient and control the function ‘ kidney is all ‘beginning of treatment and periodically thereafter. Co-administration of the drug and potassium-sparing diuretics can ’cause hyperkalemia. It requires monitoring of blood potassium concentrations. Methotrexate if used at low doses (<15 mg / week): increased toxicity ‘haematological of methotrexate due to a decrease in its renal clearance generally caused by anti-inflammatory drugs.

Check every week ‘s blood count during the first weeks of combination therapy. Increase surveillance in older patients and in the presence of renal failure although slight. Pentoxifylline: increased risk of bleeding. Carefully monitor and control more frequently bleeding time. Zidovudine: increased risk of toxicity ‘in red cell line for action on reticulocytes, with possible severe anemia occurring one week after the ‘ starting treatment with NSAIDs. Perform complete blood count and reticulocyte control every 7-14 days during treatment with NSAIDs. Sulfonylureas: NSAIDs can increase the ‘hypoglycaemic effect of sulfonylureas by saturation of plasma protein binding sites. >> Association to be evaluated carefully. Beta-blockers: treatment with NSAIDs can ‘decrease their antihypertensive effect because of ‘ inhibition of prostaglandin synthesis. Cyclosporine and tacrolimus: NSAIDs may enhance the nephrotoxicity ‘due to renal prostaglandin mediated effects. During therapy control the function ‘kidney. Thrombolytics: increased risk of bleeding. Anti-platelet agents and SSRIs (selective serotonin reuptake inhibitors): increased risk of gastrointestinal bleeding. Probenecid: can ‘increase plasma concentrations of dexketoprofen; this interaction can ‘be due to an inhibitory mechanism at the level of the renal tubule secretion and glucuronide conjugation and requires an adjustment of the dose of dexketoprofen. Cardiac glycosides: NSAIDs may increase plasma concentrations of glicosidicardioattivi. Mifepristone: there is a theoretical risk that prostaglandin synthetase inhibitors may alter the ‘efficacy of mifepristone.

Limited evidence suggests that co-administration of NSAIDs on the same day of the administration of prostaglandins does not adversely affect the effects of mifepristone or the prostaglandin on cervical ripening or contractility ‘uterine and reduce the ‘ clinical efficacy of ‘medical termination of pregnancy. Quinolone: ​​studies on ‘animal indicate that high doses of chemotherapeutic agents in combination with NSAIDs can increase the risk of seizures.

 

Side Effects
Below, they are grouped by device and listed in order of frequency, adverse reactions, possibly related with dexketoprofen trometamol, which occurred in clinical studies and post-marketing drug granules. The C max plasma levels of dexketoprofen in the formulation that the granules are superior to those reported for the tablet formulation, therefore, not ‘can exclude a potential increased risk of adverse events (gastrointestinal). Blood and lymphatic system. Very rare: neutropenia, thrombocytopenia. Disorders of the immune system. Very rare: anaphylactic reactions, including anaphylactic shock; unknown: laryngeal edema.

Metabolism and nutrition disorders. Rare: anorexia. psychiatric disorders. Uncommon: insomnia; anxiety. Nervous system disorders. Uncommon: headache, dizziness, drowsiness; Rare: paresthesia, syncope. Pathologies ‘s eye. Very rare: blurred vision. Pathologies ‘s ear and labyrinth. Uncommon: dizziness; very rare: tinnitus. Cardiac disorders. Uncommon: palpitations; very rare: tachycardia. Vascular disorders. Uncommon: hot flashes; rare: hypertension; Very rare: hypotension. Respiratory, thoracic and mediastinal disorders. Rare: bradypnea; very rare: bronchospasm, dyspnea. Gastrointestinal disorders. Common: nausea and / or vomiting, abdominal pain, diarrhea, dyspepsia; uncommon: gastritis, constipation, dry mouth, flatulence; rare: peptic ulcer, bleeding or perforation of peptic ulcer; Very rare: pancreatitis.

Hepatobiliary disorders. Rare: hepatic injury; Very rare: Hepatocellular damage; not known: hepatitis. Skin and subcutaneous tissue. Uncommon: rash; rare: rash, acne, increased sweating; very rare: Steven Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), angioedema, face edema, photosensitivity reaction ‘, itching. Musculoskeletal and connective tissue. Rare: back pain. Renal and urinary disorders. Rare: polyuria; very rare: nephritis and nephrotic syndrome; not known: Acute renal failure. Pathologies ‘s reproductive tract and breast. Rare: menstrual disorders. prostatic disorders.

General disorders and administration site disorders. Uncommon: fatigue, pain, asthenia, chills, malaise; rare: peripheral edema. Investigations. Rare: abnormalities in the function ‘liver tests. The side effects most ‘commonly seen are gastrointestinal in nature. May occur peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, particularly in the elderly. Following administration have been reported nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease. Less often, and ‘was found gastritis. In association with NSAID therapy we have been reported edema, hypertension and heart failure. The results of clinical trials and epidemiological data suggest that the ‘Use of some NSAIDs (particularly at high doses and for long periods) can ‘ be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke ). As with other NSAIDs, the following undesirable effects may appear: aseptic meningitis, which can ‘predominantly occur in patients with systemic lupus erythematosus or mixed connective tissue disease; haematological reactions (purpura, aplastic and haemolytic anemia, and rarely agranulocytosis and medullar hypoplasia).

 

Pregnancy
The medication ‘contraindicated during pregnancy and l ‘ lactation. L ‘inhibition of prostaglandin synthesis can ‘ have adverse effects on pregnancy and / or the development of ’embryo or fetus. Results of epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after ‘use of an inhibitor of prostaglandin synthesis in the early stages of pregnancy. It is believed that the risk increases with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and mortality ’embryo-fetal. Also an increase in the incidence of various malformations, including cardiovascular, and ‘been reported in animals given a prostaglandin synthesis inhibitor during the organogenesis period had been administered.

However, studies with dexketoprofen trometamol in animals have shown no toxicity ‘reproductive. During the first and second trimester of pregnancy, dexketoprofen trometamol should be administered only when strictly necessary. If dexketoprofen trometamol and ‘used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose and duration of treatment should be kept as the most ‘ lowest possible. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to: toxicity ‘cardiopulmonary (with premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which can ‘progress to renal failure with oligohydramnios; the mother and the newborn, at the end of pregnancy, to: possible prolongation of bleeding time, and antiplatelet effect which can ‘occur even at very low doses; inhibition of uterine contractions resulting in delayed or prolonged labor.

L ‘use of the medicine can ‘ damaging fertility ‘feminine and it is not recommended the administration to women who want to become pregnant. In the case of women with difficulties ‘conceiving or who are carrying out tests for infertility ‘, evaluate ‘discontinuation of dexketoprofen trometamol. Not ‘it is known whether dexketoprofen is excreted in human milk. The drug ‘contraindicated during ‘ lactation.