ENANTYUM 10BS SOLUZ 25MG 10ML

ENANTYUM 25 MG ORAL DEPARTMENT

active ingredients

Each bag of oral solution contains: dexketoprofene 25 mg as dexketoprofene tromethylamolo. Excipients with known effects: 2 g of sucrose and 20 mg of methyl parahydroxybenzoate (E 218). For the full list of excipients, see paragraph 6.1.

Excellent

Glycyrrizinate ammonium Neoesperidine-dihydrocalcone Metil parahydroxybenzoate (E 218) Sodium saccharin Macrogol 400 Lemon aroma Povidone K-90 Dioxide phosphate anidro Sodium hydrogen phosphate dihydrate Purified water

Therapeutic indications

Syntomatic treatment of short duration of acute painful affections of mild to moderate intensity, such as acute musculoskeletal pain, dysmenorrhea and dental pain. This medicine is indicated in adult patients.

Contraindications

- patients with hypersensitivity determined towards the active ingredient, or any other NSAID, or any of the excipients listed in paragraph 6.1; - patients who have developed asthma, bronchospasm, acute rhinitis, nasal polyps, hives or angioedema after exposure to substances from the mechanism of similar action (e.g. Acetylsalicylic acid, or other NSAIDs) - patients with photoallergic or phototoxic reactions known during treatment with ketoprofen or fibres; - patients with bleeding anamnesis or gastrointestinal perforation related to a previous therapy with NSAIDs; - patients with active peptic ulcer/gastrointestinal bleeding in place or any previous anamnestic bleeding, ulceration or gastrointestinal perforation; - patients with chronic dyspepsia; - patients who have other bleeding in place or clotting disorders; - patients with Crohn disease or ulcerative colitis; - patients with severe heart failure; - patients with moderate to severe renal insufficiency (clearance of creatinine

Population

Population The lower effective dose must be used for the shortest duration necessary to relieve symptoms (see paragraph 4.4). Adults: Depending on the nature and intensity of pain, the recommended dose is generally 25 mg every 8 hours. The total daily dose should not exceed 75 mg. This medicine is indicated only for short-term treatments and administration is limited to only symptomatic period. Seniors: In elderly patients it is recommended to start therapy with the lowest therapeutic dose (50 mg daily total dose). The dosage can be increased so as to reach the recommended one for the adult only after a good tolerance has been established. Due to the risk profile (see paragraph 4.4), the elderly must be closely monitored. Epathetic insufficiency Patients with mild to moderate liver dysfunction should start therapy at reduced doses (50 mg the total daily dose) under strict medical control. Dexketoprofen should not be used in patients with severe liver dysfunction. Renal insufficiency In patients with mild renal insufficiency (cantonance of creatinine 60 - 89 ml/min) the initial dosage must be reduced to 50 mg of total daily dose (see paragraph 4.4). Dexketoprofen should not be used in patients with mild to severe renal dysfunction (creatiny ≤59 ml/min) (see paragraph 4.3). Pediatric population: Dexketoprofen was not studied in children and adolescents. Therefore, safety and effectiveness in children and adolescents were not established and the product should not be used in children and adolescents. Method of administration Oral use. The oral solution must be taken directly from the envelope or after mixing the whole content in a water bidder. Once the envelope is opened, the entire content must be consumed. The concomitant administration of food delays the rate of absorption of the drug (see the pharmacokinetic properties), so in case of acute pain it is recommended to administer the drug at least 15 minutes before meals.

Conservation

This medicine does not require special precautions for conservation.

Warnings

Use with precaution in patients with anamnesi of allergic conditions. Concurrent use of dexketoprofen should be avoided with other NSAIDs, including selective cyclooxygenase-2 inhibitors. Undesirable effects can be minimized using the lowest effective dose for the time strictly necessary to control symptoms (see paragraph 4.2 and gastrointestinal and cardiovascular risks below). Gastrointestinal safety Blood, ulceration or potentially fatal gastrointestinal perforation have been reported with all NSAIDs, at any time during treatment, with or without premonitory symptoms or previous anamnesi of serious gastrointestinal events. When dexketoprofene is administered in patients with bleeding or gastrointestinal ulceration, therapy must be immediately interrupted. The risk of bleeding, ulceration or gastrointestinal perforation increases with the increase of the dosage of NSAIDs in patients with pregress ulcer, especially if complicated by hemorrhage or perforation (see paragraph 4.3) and in the elderly. Use in the elderly: the elderly have a greater frequency of adverse reactions to the NSAIDs, especially bleeding and gastrointestinal perforation that can be fatal (see paragraph 4.2). These patients must begin treatment with the minimum dose available. As with all NSAIDs, before starting treatment with dexketoprofene, it is necessary to investigate esophagitis, gastritis and/or peptic ulcers and ensure their total healing. Patients with gastrointestinal or anamnesi symptoms of gastrointestinal disease must be carefully monitored for the appearance of digestive disorders, especially gastrointestinal bleeding. NSAIDs should be given with caution to patients with anamnes of gastrointestinal pathologies ( ulcerative colitis, Crohn's disease), since these conditions may be exacerbated (see paragraph 4.8). Concurrent use of protective agents (e.g. misoprostol or protonic pump inhibitors) must be considered for these patients and patients who receive a low concomitant dose of aspirin or other drugs that may increase the gastrointestinal risk (see below and paragraph 4.5). Patients with an anamnesi of gastrointestinal toxicity, especially if elderly, must report any unusual abdominal symptoms (especially gastrointestinal bleeding), especially in the early stages of treatment. Precaution is recommended in patients who are administered at the same time medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors and anti-aggregating agents such as aspirin (see paragraph 4.5). Renal safety Use carefully in patients with compromised kidney function. In these patients the use of NSAIDs can cause deterioration of kidney function, fluid retention and edema. Caution is needed for increased risk of nephrotoxicity, even in patients in diuretic therapy or who risk developing hypovolemia. During treatment it is necessary to ensure adequate intake of liquids to prevent dehydration and the risk of kidney toxicity. Like all NSAIDs, the product can cause an increase in azotemia and creatininemia. As with other prostaglandin synthesis inhibitors, undesirable effects can occur on the kidney that can lead to glomerular nephritis, interstitial nephritis, kidney papillar necrosis, nephrosic syndrome and acute kidney failure. Senior patients are the most exposed to the risk of kidney failure (see paragraph 4.2). Epathetic safety Caution is needed in patients with impairment of liver function. Like other NSAIDs, it can cause small transient increments of some parameters of liver function, and also significant increases of GOT and GPT. In the event of a significant increase in these parameters, therapy must be interrupted. Senior patients are the most exposed at risk of liver failure (see paragraph 4.2). Cardiovascular and cerebrovascular safety For patients with an anamnesi of hypertension and/or mild to moderate heart failure, appropriate monitoring is required. Particular caution should be given in cardiopathic patients, especially if with heart failure anamnesis since there is increased risk of heart failure, since fluid and edema were reported in conjunction with the use of NSAIDs. Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially high doses and protracted therapies) may be associated with a slight increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There is no sufficient data to exclude such risk for dexketoprofene. Therefore patients with uncontrolled hypertension, congestive heart failure, established ischemic cardiopathy, peripheral arteriopathy and/or cerebrovascular pathologies should be treated with dexketoprofen only after careful evaluation. Analogue attention should be paid before starting long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking). All non-selective NSAIDs are able to inhibit piastrinic aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. The use of dexketoprofen is therefore not recommended in patients receiving another therapy that interferes with hemostasis, such as warfarin or other cumarinics or eparine (see paragraph 4.5). Older patients are more likely to have alterations in the cardiovascular function (see paragraph 4.2). Skin reactions Severe skin reactions (some of which fatal), including exfoliative dermatitis, Stevens-Johnson syndrome and epidermal toxic necrolysis, have been reported, very rarely, in association with the use of NSAIDs (see paragraph 4.8). In the early stages of therapy, patients seem at the highest risk of reaction onset, in most cases, within the first month of treatment. At the first appearance of skin rash, mucosa lesions or any other symptom of hypersensitivity, Enantyum therapy should be interrupted. Masking the symptoms of underlying infections Dexketoprofen can mask the symptoms of infection, which may delay the start of proper treatment and thus worsen the outcome of the infection. This was observed in bacterial pneumonia acquired in communities and bacterial complications of chickenpox. When this medicine is administered for pain relief related to infection, it is recommended to monitor the infection. In non-hospital contexts, the patient should contact the doctor if symptoms persist or worsen. Other information Particular caution is required in patients with: - congenital abnormalities of porphyrin metabolism (e.g. acute intermittent porphyria); - dehydration; - immediately after a major surgery. If the doctor considers long-term therapy necessary with dexketoprofene, hepatic, kidney and hemochrome should be checked regularly. Strict reactions from acute hypersensitivity (e.g. anaphylactic shock) have been observed in rare cases. Treatment should be interrupted by the appearance of the first manifestation of severe hypersensitivity reactions after taking dexketoprofene. Depending on the symptoms, immediately start the necessary medical procedures, with qualified medical personnel. Patients with asthma associated with chronic rhinitis, chronic sinusitis and/or nasal polypoxes have a greater risk of allergy to acetylsalicylic acid and/or NSAIDs than the rest of the population. The administration of this medicine may cause asthma or bronchospasm attacks especially in allergic to acetylsalicylic acid or NSAIDs (see paragraph 4.3). In exceptional cases chickenpox can be associated with infectious complications of skin and soft tissues. To date, a role of NSAIDs cannot be excluded in the aggravation of such infections, so it is advisable to avoid the use of dexketoprofen in patients with chickenpox. Dexketoprofene should be administered with caution to patients suffering from hematopoietic disorders, systemic lupus erythematous or mixed connective tissue disease. By concurrent intake of alcohol, side effects related to the active ingredient, particularly those affecting the gastrointestinal tract or central nervous system, can increase with the use of NSAIDs. This medicine may cause allergic reactions (also delayed) as it contains methyl parahydroxybenzoate (E 218). This medicine contains sucrose. Patients suffering from rare hereditary problems of fructose intolerance, glucose-galactosis mal absorption or isomaltase sucrasis failure should not take this medicine. To consider in people with diabetes mellitus. This medicine contains less than 1 mmol of sodium (23 mg) per bag, i.e. it is essentially "without sodium".

Interactions

The following interactions are characteristics of non-steroidal anti-inflammatory drugs (NSAID) in general: Other NSAIDs (including selective oxygenase-2 inhibitors) and high doses of salicylates (≥3 g/die): simultaneous administration of multiple NSAIDs can increase the risk of gastrointestinal ulceration and bleeding due to a synergistic effect. - Antiagulants: NSAIDs can enhance the effects of anticoagulants, such as warfarin (see paragraph 4.4), due to the high plasma protein bond of dexketoprofene, inhibition of pyasternic function and damage to gastro-duodenal mucosa. If it is not possible to avoid the association, rigorous clinical observation and monitoring of laboratory parameters are necessary. - Eparine: increased risk of hemorrhage (due to the inhibition of the pyasternic function and the damage to gastrointestinal mucosa). If it is not possible to avoid the association, rigorous clinical observation and monitoring of laboratory parameters are necessary. - Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see paragraph 4.4). - Lithium (described with many NSAIDs): NSAIDs increase blood levels of lithium with the risk of reaching toxic values (renal excretion of decreased lithium). Therefore, this parameter requires careful monitoring at the beginning, during adjustment and at the end of treatment with dexketoprofene. - Metotressed if used at high doses (≥ 15 mg/week): increased hematological toxicity of metotressate due to a decrease in its kidney clearance, in general with NSAIDs. - Idantoins and sulfonamides: the toxic effects of these substances can be enhanced. Associations requiring caution: - Diuretics, ACE inhibitors, aminoglycoside antibiotics and antagonists of angiotensin receptor II: dexketoprofen can reduce the effect of diuretics and antihypertensive drugs. In some patients with impaired kidney function (for example, dehydrated patients or elderly patients with impaired kidney function), concomitant administration of agents that inhibit cyclooxygenase and ACE inhibitors, antagonists of angiotensin II receptor or aminoglycoside antibiotics may cause further deterioration of kidney function, usually reversible. In case of concomitant prescription of dexketoprofene and diuretic, it is essential to ensure proper hydration of the patient and to control the kidney function both at the beginning of the treatment and periodically afterwards. Concurrent administration of Enantyum and potassium-saving diuretics can cause hypercalemia. It is necessary to monitor blood potassium concentrations (see paragraph 4.4). - Metotressed if used at low doses (

Effects

The adverse events reported as possibly linked to dexketoprofene in clinical trials (formulation in tablets), as well as adverse reactions reported after the marketing of Enantyum oral solution in sachet are included in the table below, grouped by apparatus and listed in frequency order: Since plasma levels C_max dexketoprofen for oral formulation are higher than those reported for formulation in tablets, it is not possible to exclude a potential increase in the risk of adverse events (gastrointestinal) .

CLASS/APPARATE/ORGANO	Municipality (≥1/100 a	Not common (≥1/1.000 a	Rare (≥1/10.000 a	Very rare (
Hemolinphatic system pathologies	---	---	---	Neutropenia, thrombocytopenia
Immune system disorders	---	---	Larynx Edema	Anaphylactic reactions, including anaphylactic shock
Disorders of metabolism and nutrition	---	---	Anorexia	---
Psychiatric disorders	---	Insomnia, anxiety	---	---
Diseases of the nervous system	---	Cephalea, drowsiness dizziness	Opinion , syncope	---
Pathologies of the eye	---	---	---	View blur
Ear and labyrinth pathologies	---	Vertigo	---	Tinnitus
Heart disease	---	Palpitations	---	Tachycardia
Vascular diseases	---	Red	Hypertension	Hypotension
Respiratory, chest and mediastinic pathologies	---	---	Bradipnea	Broncospasmo, dispnea
Gastrointestinal diseases	Nausea and/or vomiting, abdominal pain, diarrhea, dyspepsia	Gastrite, stipsi, dry mouth, flatulence	Peptic ulcer, hemorrhage or perforation from peptic ulcer (see paragraph 4.4)	Pancreatis
Hepatobiliary diseases	---	---	Hepatocellular year
Pathologies of skin and subcutaneous tissue	---	Skin rash	Orticaria, acne, increased sweating	Stevens Johnson Syndrome, toxic epidermal neccrolysis ( Lyell syndrome), angioedema, facial edema, photosensitivity reaction, itching
Skeletal muscle and connective tissue system pathologies	---	---	Dorsal pain	---
Kidney and urinary pathologies	---	---	Acute renal insufficiency, Polyuria	Nephritis or nephrosic syndrome
Pathologies of the reproductive apparatus and of the breast	---	---	Menstrual disorder, prostate pathology	---
Systemic pathologies and disorders in the administration	---	Affection, pain, asthenia, shivers, sense of malaise	Peripheral edema	---
Diagnostic examinations	---	---	Anomaly in liver function tests	---

The most commonly observed side effects are gastrointestinal. Peptic ulcers, perforation or gastrointestinal bleeding may occur, sometimes fatal especially in the elderly (see paragraph 4.4 Warnings and precautions for use). As a result of the administration, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, ematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see paragraph 4.4) were reported. With less frequency gastritis was detected. In association with NSAID therapy, edema, hypertension and heart failure were reported. As with other NSAIDs, the following side effects may occur: aseptic meningitis, which can occur more in patients with systemic erythematous lupus or mixed connective tissue disease; hematological reactions (porpora, aplastic anemia and hemolytics, and more rarely agranulocytosis and midollar hypoplasia). Bollose reactions including Stevens Johnson syndrome and toxic epidermal necrolysis (very rare). The results of clinical trials and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long periods) may be associated with a slight increase in the risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see paragraph 4.4). Reporting of suspicious adverse reactions It is important to report suspicious adverse reactions after authorization of the drug. Allows continuous monitoring of the benefit/risk ratio of the drug. Health professionals are asked to report any suspected adverse reaction through the national reporting system at the address http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

Overdosing

Syntomatology derived from overdose is not known. Similar medicinal products have caused gastrointestinal disorders (vomite, anorexia, abdominal pain) and neurological disorders (sonnolence, dizziness, disorientation, headache). In case of accidental or excessive intake, immediately take appropriate symptomatic therapy according to the clinical conditions of patients. Within an hour it is necessary to administer activated charcoal if more than 5 mg/kg were ingested by an adult or child. Dexketoprofene tromethylamolo can be eliminated by dialysis.

Dexketoprofene is contraindicated during the third trimester of pregnancy and during breastfeeding (see paragraph 4.3).

Pregnancy

The inhibition of prostaglandin synthesis can have negative effects on pregnancy and/or on the development of embryo or fetus. Results of epidemiological studies suggest an increased risk of spontaneous abortion and heart and gastroschisis malformation after the use of an inhibitor of prostaglandin synthesis in the early stages of pregnancy. The absolute risk of heart failure had increased from less than 1% to about 1.5%. It is believed that the risk increases with dose and duration of therapy. In animals, the administration of prostaglandin synthesis inhibitors showed an increase in pre- and post-system loss and embryo-fetal mortality. In addition, an increase in the incidence of various malformations, including cardiovascular malformations, was reported in animals that had been given inhibitors of prostaglandin synthesis during the organogenetic period (see paragraph 5.3). During the first and second trimester of pregnancy dexketoprofen should not be administered unless strictly necessary. If dexketoprofene is used by a woman waiting for conception or during the first and second trimester of pregnancy, the dose and duration of treatment must be maintained as low as possible. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to: - cardiopulmonary toxicity (with premature closure of arterial duct and pulmonary hypertension); - kidney dysfunction, which can progress in kidney failure with oligoidramnios; the mother and the newborn, at the end of pregnancy, to: - possible prolongation of bleeding time, an anti-aggregating effect that can also occur at very low dosages; - inhibition of uterine contractions, resulting in delay or extension of labor.

Food

It is not known whether dexketoprofene is excreted in breast milk. Its use is contraindicated during breastfeeding (see paragraph 4.3).

Fertility

As with other NSAIDs, the use of dexketoprofen can damage female fertility and it is not recommended that women wish to have a pregnancy. In the case of women with difficulties of conception or who are carrying out infertility examinations, assess the interruption of the administration of dexketoprofen.

Source: Farmadati