Enantyum 25mg 20 coated tablets

Enantyum 25mg 20 coated tablets is a nonsteroidal anti-inflammatory drug (NSAID) indicated for the symptomatic treatment of mild to moderate pain . Each tablet contains dexketoprofen 25 mg , an active ingredient known for its effectiveness in reducing musculoskeletal pain, dysmenorrhea and dental pain. The tablets are coated to ensure easier intake and better gastric tolerability. Enantyum is formulated to offer rapid pain relief, thanks to its targeted action and its ability to inhibit the synthesis of prostaglandins, chemicals responsible for inflammation and pain. This drug is particularly useful for those looking for an effective and fast option to manage acute pain.

ACTIVE INGREDIENTS

Active ingredients contained in Enantyum 25mg 20 coated tablets - What is the active ingredient of Enantyum 25mg 20 coated tablets?

Each tablet contains: dexketoprofen 25 mg as dexketoprofen trometamol. For the full list of excipients, see section 6.1.

EXCIPIENTS

Composition of Enantyum 25mg 20 coated tablets - What does Enantyum 25mg 20 coated tablets contain?

Tablet core: -maize starch, -microcrystalline cellulose, -sodium starch glycolate, -glycerol distearate. Film coating: - dry lacquer composed of: - hypromellose, - titanium dioxide, - macrogol 6000; -propylene glycol.

DIRECTIONS

Therapeutic indications Enantyum 25mg 20 coated tablets - Why is Enantyum 25mg 20 coated tablets used? What is it used for?

Symptomatic treatment of painful conditions of mild to moderate intensity, such as musculoskeletal pain, dysmenorrhea, dental pain.

CONTRAINDICATIONS SIDE EFFECTS

Contraindications Enantyum 25mg 20 coated tablets - When should Enantyum 25mg 20 coated tablets not be used?

Enantyum tablets should not be used in the following cases: - patients with hypersensitivity to the active substance, or to other NSAIDs, or to any of the excipients listed in section 6.1; - patients in whom active substances with similar action (e.g. acetylsalicylic acid, or other NSAIDs) trigger attacks of asthma, bronchospasm, acute rhinitis, or are the cause of nasal polyps, urticaria or angioneurotic oedema; - known photoallergic or phototoxic reactions during treatment with ketoprofen or fibrates; - patients with a history of gastrointestinal bleeding or perforation in relation to previous NSAID therapy; - patients with active peptic ulcer/gastrointestinal bleeding or a history of gastrointestinal bleeding, ulceration or perforation; - patients with chronic dyspepsia; - patients who have other active bleeding or coagulation disorders; - patients with Crohn's disease or ulcerative colitis; - patients with severe heart failure; - patients with moderate to severe renal insufficiency (creatinine clearance ≤ 59 ml/min); - patients with severe hepatic impairment (Child-Pugh score 10 - 15); - patients with haemorrhagic diathesis and other coagulation disorders; - patients with severe dehydration (caused by vomiting, diarrhoea or insufficient fluid intake); - during the third trimester of pregnancy and breast-feeding (see section 4.6).

DOSAGE

Quantity and method of taking Enantyum 25mg 20 coated tablets - How to take Enantyum 25mg 20 coated tablets?

Dosage Adults Depending on the nature and severity of the pain, the recommended dose 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 minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4). Enantyum tablets are not indicated for long-term treatment and administration should be limited to the symptomatic period only. Elderly In elderly patients, it is recommended to start therapy at the lower end of the dosage range (50 mg total daily dose). The dosage may be increased to that used for the general population only after good general tolerability has been established. Hepatic impairment Patients with mild to moderate hepatic impairment should start therapy at reduced doses (50 mg total daily dose) and should be subjected to close medical supervision. Enantyum tablets should not be used in patients with severe hepatic impairment. Renal impairment In patients with mild renal impairment (creatinine clearance 60 - 89 ml/min), the initial dosage should be reduced to 50 mg total daily dose (see section 4.4). Enantyum tablets should not be used in patients with moderate to severe renal impairment (creatinine clearance ≤ 59 ml/min) (see section 4.3). Paediatric population Enantyum tablets have 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. Method of administration The tablet should be swallowed with a sufficient amount of liquid (e.g. a glass of water). Concomitant administration of food delays the rate of absorption of the drug (see section “Pharmacokinetic Properties”), therefore in case of acute pain it is recommended that administration occurs at least 30 minutes before meals.

CONSERVATION

Storage Enantyum 25mg 20 coated tablets - How to store Enantyum 25mg 20 coated tablets?

PVC-aluminium blister: Do not store above 30°C. Store in the original package to protect from light. Aclar-aluminium blister: This medicine does not require any special storage conditions.

WARNINGS

Warnings Enantyum 25mg 20 coated tablets - About Enantyum 25mg 20 coated tablets it is important to know that:

Use with caution in patients with a history of allergic conditions. Concomitant use of Enantyum and other NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided. Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and the gastrointestinal and cardiovascular risks below). Gastrointestinal safety Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at various stages of treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. If gastrointestinal bleeding or ulceration occurs in patients receiving Enantyum, the treatment should be discontinued. The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal (see section 4.2). These patients should start treatment with the lowest possible dose. As with all NSAIDs, before starting treatment with dexketoprofen, previous history of oesophagitis, gastritis and/or peptic ulcer should be enquired about and ensure complete healing. Patients with gastrointestinal symptoms or a history of gastrointestinal disorders should be carefully monitored for digestive disturbances, especially gastrointestinal bleeding. NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated (see section 4.8). Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients receiving concomitant low dose acetylsalicylic acid or other drugs likely to increase gastrointestinal risk (see below and section 4.5). 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 is 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 acetylsalicylic acid (see section 4.5). Renal safety To be used with caution in patients with impaired renal function. In these patients, the use of NSAIDs may result in worsening of renal function, fluid retention and oedema. Caution is also required in patients receiving diuretic therapy or in those patients who may develop hypovolaemia, due to an increased risk of nephrotoxicity. During treatment, adequate fluid intake should be ensured to prevent dehydration associated with a possible increase in renal toxicity. Like all NSAIDs, the medicinal product may cause an increase in azotemia and creatininemia. As with other inhibitors of prostaglandin synthesis, it may be associated with adverse effects on the kidney that may lead to glomerular nephritis, interstitial nephritis, renal papillary necrosis, nephrotic syndrome and acute renal failure. Elderly patients are more likely to have reduced renal function (see section 4.2). Hepatic safety To be used with caution in patients with impaired liver function. Like other NSAIDs, the medicinal product may cause slight transient increases in some liver parameters and also significant increases in AST and ALT. If a significant increase in these parameters occurs, treatment should be discontinued. Elderly patients are more likely to suffer from reduced liver function (see section 4.2). Cardiovascular and cerebrovascular safety Appropriate monitoring and advice are necessary in patients with a history of hypertension and/or mild to moderate heart failure. Particular caution is required in patients with a history of cardiac disease, especially those with a history of heart failure. An increased risk of triggering heart failure has been reported in these patients, since fluid retention and oedema have been reported in association with NSAID treatment. 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 a similar risk for dexketoprofen. Consequently, patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with dexketoprofen after careful consideration. Similar consideration should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking). All non-selective NSAIDs are capable of inhibiting platelet aggregation and prolonging bleeding time by inhibiting prostaglandin synthesis. Therefore, the use of dexketoprofen in patients receiving other treatments that interfere with haemostasis, such as warfarin or other coumarins or heparins is not recommended (see section 4.5). Elderly patients are more likely to have reduced cardiovascular function (see section 4.2). 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. Patients appear to be at highest risk of these reactions early in therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Treatment with Enantyum should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Masking of symptoms of underlying infections Dexketoprofen may mask the symptoms of infection, which may delay initiating adequate treatment and therefore worsen the outcome of the infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When this medicinal product is administered for the relief of infection-related pain, monitoring for infection is advised. In non-hospital settings, the patient should seek medical attention if symptoms persist or worsen. In exceptional cases, chickenpox may be associated with serious infectious complications of the skin and soft tissue. A role of NSAIDs in the aggravation of these infections cannot be ruled out to date, therefore it is advisable to avoid the use of Enantyum in patients with chickenpox. Further information Particular caution is required in patients: - with a congenital disorder of porphyrin metabolism (e.g. acute intermittent porphyria); - with dehydration; - immediately after major surgery. If the doctor considers long-term therapy with dexketoprofen to be necessary, liver and kidney function and blood counts should be monitored regularly. Severe acute hypersensitivity reactions (e.g. anaphylactic shock) have been observed very rarely. Treatment should be stopped at the first signs of severe hypersensitivity following the intake of Enantyum. Any necessary medical procedures should be initiated by healthcare professionals based on symptoms. Patients with asthma associated with chronic rhinitis, chronic sinusitis, and/or nasal polyposis have a higher risk of allergy to acetylsalicylic acid and/or NSAIDs than the rest of the population. Administration of this medicinal product may cause asthma attacks or bronchospasm, particularly in subjects allergic to acetylsalicylic acid or NSAIDs (see section 4.3). Enantyum should be administered with caution to patients suffering from haematopoietic disorders, systemic lupus erythematosus or in the presence of connective tissue diseases. This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially “sodium-free”. Paediatric population The safety of use in children and adolescents has not been established.

INTERACTIONS

Interactions Enantyum 25mg 20 coated tablets - Which medicines or foods can modify the effect of Enantyum 25mg 20 coated tablets?

The following interactions are characteristic of nonsteroidal anti-inflammatory drugs (NSAIDs) in general: Combinations which are not advisable: - Other NSAIDs (including selective cyclooxygenase-2 inhibitors) and high doses of salicylates (≥ 3 g/day): the concomitant administration of several NSAIDs may increase the risk of ulcers and gastrointestinal bleeding due to a synergistic effect. - Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin (see section 4.4) due to the high plasma protein binding of dexketoprofen and the inhibition of platelet function and damage to the gastroduodenal mucosa. If the association cannot be avoided, careful clinical observation and monitoring of laboratory parameters should be performed. - Heparins: increased risk of haemorrhage (due to inhibition of platelet function and damage to the gastroduodenal mucosa). If the association cannot be avoided, careful clinical observation and monitoring of laboratory parameters is necessary. - Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4). - Lithium (described with several NSAIDs): NSAIDs increase blood levels of lithium which may reach toxic values ​​(decreased renal excretion of lithium). This parameter therefore requires careful monitoring during the institution, adjustment and interruption of treatment with dexketoprofen. - Methotrexate, used at high doses such as 15 mg/week or more: increased haematological toxicity of methotrexate due to a decrease in its renal clearance, caused by anti-inflammatory drugs in general. - Hydantoins and sulfonamides: the toxic effects of these substances may be potentiated. Combinations requiring caution: - Diuretics, ACE inhibitors, aminoglycoside antibiotics and angiotensin II receptor antagonists: dexketoprofen may reduce the effect of diuretics and other antihypertensive drugs. In some patients with reduced renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the concomitant administration of agents that inhibit cyclooxygenase and ACE inhibitors, angiotensin II receptor antagonists or aminoglycoside antibiotics may result in further deterioration of renal function, which is usually reversible. In case of combined prescription of dexketoprofen with a diuretic, it is essential to ensure that the patient is adequately hydrated and to monitor renal function at the beginning of treatment (see section 4.4 Special warnings and precautions for use). - Methotrexate, used at doses lower than 15 mg/week: increased haematological toxicity of methotrexate due to a decrease in its renal clearance caused by anti-inflammatory drugs in general. Weekly blood count in the first weeks of the association. Increased surveillance, not only for elderly patients, but also in cases of even mild renal insufficiency. - Pentoxifylline: increased risk of haemorrhage. Increase clinical monitoring and check bleeding time more frequently. - Zidovudine: risk of increased toxicity to the erythrocyte line due to the action on reticulocytes, with the onset of severe anaemia one week after the start of treatment with NSAIDs. Check the complete blood count and reticulocytes every one or two weeks during treatment with NSAIDs. - Sulfonylureas: NSAIDs may increase the hypoglycemic effect of sulfonylureas by displacement from binding sites on plasma proteins. Combinations to be taken into consideration: - Beta-blockers: treatment with NSAIDs may decrease their antihypertensive effect due to inhibition of prostaglandin synthesis. - Ciclosporin and tacrolimus: NSAIDs may enhance their nephrotoxicity due to effects mediated by renal prostaglandins. Renal function should be monitored during combination therapy. - Thrombolytics: increased risk of haemorrhage. - Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4). - Probenecid: may increase plasma concentrations of dexketoprofen; this interaction may be due to an inhibitory mechanism at the level of renal tubular secretion and glucuronide conjugation and requires dose adjustment of dexketoprofen. - Cardiac glycosides: NSAIDs may increase plasma concentrations of glycosides. - Mifepristone: There is a theoretical risk that prostaglandin synthetase inhibitors may alter the efficacy of mifepristone. Limited evidence suggests that concomitant administration of NSAIDs on the same day as prostaglandins does not adversely affect the effects of mifepristone or prostaglandins on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medical termination of pregnancy. - Quinolone antibiotics: Animal studies indicate that high doses of quinolones in combination with NSAIDs may increase the risk of convulsions. - Tenofovir: Concomitant use with NSAIDs may increase blood urea nitrogen and creatinine, therefore renal function should be monitored to control for a possible synergistic influence on renal function. - Deferasirox: Concomitant use with NSAIDs may increase the risk of gastrointestinal toxicity. Close clinical monitoring is required when deferasirox is administered with these substances. - Pemetrexed: concomitant use with NSAIDs may reduce the elimination of pemetrexed, therefore caution should be exercised when administering higher doses of NSAIDs; in patients with mild to moderate renal impairment (creatinine clearance between 45 and 79 ml/min), concomitant administration of pemetrexed with NSAIDs should be avoided for 2 days before and 2 days after pemetrexed administration.

SIDE EFFECTS

Like all medicines, Enantyum 25mg 20 coated tablets can cause side effects - What are the side effects of Enantyum 25mg 20 coated tablets?

The table below, divided by system organ class and listed in order of frequency, reports the adverse events, probably related to dexketoprofen, which occurred during the course of clinical studies and after the marketing of Enantyum tablets:

The most common adverse effects are gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, especially in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration (see section 4.4 "Special warnings and precautions for use"). Less frequently, gastritis has been observed. Oedema, hypertension and cardiac failure have been reported in association with NSAID therapy. As with other NSAIDs, the following undesirable effects may occur: aseptic meningitis, which may occur predominantly in patients with systemic lupus erythematosus or connective tissue disease; haematological reactions (purpura, aplastic and haemolytic anaemia, and rarely agranulocytosis and bone marrow hypoplasia). Bullous reactions, including Stevens Johnson syndrome and toxic epidermal necrolysis (very rare). Clinical trial and epidemiological data suggest that the use of some NSAIDs (particularly at high doses and in long-term treatment) may increase the risk of serious adverse reactions. duration) may be associated with a modest increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4). Reporting of suspected adverse reactions Reporting suspected adverse reactions that occur after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

OVERDOSE

Overdose Enantyum 25mg 20 coated tablets - What are the risks of Enantyum 25mg 20 coated tablets in case of overdose?

The symptoms following overdose are unknown. Similar drugs have caused gastrointestinal (vomiting, anorexia, abdominal pain) and neurological (drowsiness, dizziness, disorientation, headache) disorders. In case of accidental or excessive intake, immediately adopt an appropriate symptomatic therapy based on the clinical condition of the patient. Activated charcoal should be administered within one hour if more than 5 mg/kg have been ingested by an adult or a child. Dexketoprofen can be eliminated by dialysis.

PREGNANCY AND BREASTFEEDING

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking Enantyum 25mg 20 coated tablets.

Enantyum tablets are contraindicated during the third trimester of pregnancy and during breast-feeding. (see section 4.3). Pregnancy Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Results of epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiac malformations was increased from less than 1%, up to approximately 1.5%. The risk was believed to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to result in increased pre- and post-implantation loss and embryo-foetal mortality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period. However, animal studies with dexketoprofen have not indicated reproductive toxicity (see section 5.3). From the 20th ^week of pregnancy onwards, the use of dexketoprofen may cause oligohydramnios resulting from fetal renal dysfunction. This condition may be encountered soon after initiation of treatment and is usually reversible upon discontinuation of treatment. In addition, there have been reports of constriction of the ductus arteriosus following treatment in the second trimester, most of which resolved after discontinuation of treatment. Therefore, during the first and second trimester of pregnancy, dexketoprofen should not be administered unless clearly necessary. If dexketoprofen is 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 low as possible. Following exposure to dexketoprofen for several days from the 20th ^week of gestation onwards, antenatal monitoring for oligohydramnios and constriction of the ductus arteriosus should be considered. Treatment with dexketoprofen should be discontinued if oligohydramnios or constriction of the ductus arteriosus is observed. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to: - cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension), - renal dysfunction (see above); the mother and the neonate, at the end of pregnancy, to: - possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses, - inhibition of uterine contractions resulting in delayed or prolonged labor. Breast-feeding It has not been established whether dexketoprofen is secreted in human milk. Enantyum is contraindicated during breastfeeding (see section 4.3). Fertility As with other NSAIDs, the use of Enantyum may impair female fertility and is not recommended in women attempting to conceive. Discontinuation of dexketoprofen treatment should be considered in women who have difficulties conceiving or who are undergoing investigation of infertility.

DRIVING AND USE OF MACHINERY

Taking Enantyum 25mg 20 coated tablets before driving or using machines - Does Enantyum 25mg 20 coated tablets affect driving or using machines?

Enantyum tablets may cause side effects such as dizziness, visual disturbances or drowsiness. In such cases the ability to react, drive a vehicle or operate machinery may be impaired.