Package Insert: Information for the User

Enantyum 50 mg/2 ml injectable solution and for infusion

dexketoprofen

Read this package insert carefully before starting to use this medication because it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you and should not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist even if they are not listed in this package insert. See section 4.

6. Contents of the pack and additional information.

Enantyum is an analgesic belonging to the family of nonsteroidal anti-inflammatory drugs (NSAIDs).

It is indicated for the symptomatic treatment of moderate to severe acute pain such as postoperative pain, intense renal colic (severe kidney pain), and lower back pain (lumbago), when oral administration is not appropriate.

No use Enantyum:

-If you are allergic to dexketoprofen or any of the other components of this medication (listed in section 6);

-If you are allergic to acetylsalicylic acid or another nonsteroidal anti-inflammatory;

-If you have asthma or have had asthma attacks, acute rhinitis (a short period of nasal mucosa inflammation), nasal polyps (fleshy formations in the nasal cavity due to allergy), urticaria (skin eruption), angioedema (swelling of the face, eyes, lips, or tongue, or difficulty breathing) or wheezing (noisy breathing due to bronchial spasm) after taking acetylsalicylic acid or another nonsteroidal anti-inflammatory;

-If you have had photoallergic or phototoxic reactions (a special form of skin redness or burns exposed to sunlight) during the use of ketoprofen (a nonsteroidal anti-inflammatory) or fibrates (medicines used to reduce blood fat levels);

-If you have peptic ulcers, stomach or intestinal bleeding, or have had stomach or intestinal bleeding in the past;

• If you have digestive problems (e.g. indigestion, stomach burning)
• If you have or have had stomach or duodenal bleeding or perforation due to previous use of a nonsteroidal anti-inflammatory drug (NSAID) used for pain;
• If you have chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis);
• If you have severe heart failure, moderate to severe renal insufficiency, or severe liver insufficiency;
• If you have bleeding disorders or blood clotting disorders;
• If you are severely dehydrated (have lost a lot of body fluid) due to vomiting, diarrhea, or inadequate fluid intake;
• Are in the third trimester of pregnancy or breastfeeding.

Warnings and Precautions

Consult your doctor or pharmacist before starting to use Enantyum

• If you have had chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease);
• If you suffer or have suffered from stomach or intestinal problems;
• If you are taking simultaneously medications that increase the risk of gastrointestinal ulcers or bleeding, e.g. oral corticosteroids, some antidepressants (type ISRS: Selective Serotonin Reuptake Inhibitors), agents that prevent blood clotting such as acetylsalicylic acid or anticoagulants such as warfarin. In these cases, consult your doctor before taking Enantyum: your doctor may prescribe an additional medication to protect your stomach (e.g. misoprostol or other medications that block stomach acid production);
• If you have heart problems, a history of strokes ("cerebrovascular accident"), or think you may be at risk for these conditions (e.g. high blood pressure, diabetes, high cholesterol, or smoker). You should consult your treatment with your doctor or pharmacist. Medications like Enantyum can be associated with a small increase in the risk of suffering heart attacks ("myocardial infarction") or strokes ("cerebrovascular accident"). This risk is higher when using high doses and prolonged treatments. Do not exceed the recommended dose or treatment duration;
• If you are an elderly patient, as you may be more likely to experience adverse effects (see section 4). If these occur, consult your doctor immediately;
• If you suffer from any allergy or have had allergy problems in the past;
• If you have kidney, liver, or heart diseases (hypertension and/or heart failure), fluid retention, or have had these problems in the past;
• If you are taking diuretics or suffer from dehydration and reduced blood volume due to excessive fluid loss (e.g. excessive urination, diarrhea, or vomiting);
• If you are a woman with fertility problems (Enantyum may reduce your fertility, so do not use it if you are planning to become pregnant or undergoing fertility studies);
• If you are in the first or second trimester of pregnancy;
• If you have a disorder in blood and blood cell formation;
• If you have systemic lupus erythematosus or mixed connective tissue disease (diseases of the immune system that affect connective tissue);
• If you have an infection; see the "Infections" heading below;
• If you suffer from asthma, combined with rhinitis or chronic sinusitis, and/or nasal polyps, you have a higher risk of having an allergy to acetylsalicylic acid and/or NSAIDs than the general population. The administration of this medication may cause asthma attacks or bronchospasm, particularly in patients allergic to acetylsalicylic acid or NSAIDs.

Infections

Enantyum may mask the signs of an infection, such as fever and pain. Therefore, it is possible that Enantyum may delay the appropriate treatment of the infection, which may increase the risk of complications. This has been observed in pneumonia caused by bacteria and bacterial skin infections related to chickenpox. If you take this medication while having an infection and the infection symptoms persist or worsen, consult a doctor without delay.

During chickenpox, it is recommended to avoid using this medication.

Children and Adolescents

Enantyum has not been studied in children or adolescents. Therefore, safety and efficacy have not been established, and the product should not be used in children or adolescents.

Use of Enantyum with Other Medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including those purchased without a prescription. Some medications should not be taken together. Other medications may require a dose change if taken together.

It is especially important to inform your doctor, dentist, or pharmacist if, in addition to Enantyum, you are taking any of the following medications:

Non-recommended associations:

-Acetylsalicylic acid, corticosteroids, and other nonsteroidal anti-inflammatory drugs

-Warfarin, heparin, and other medications used to prevent blood clotting

-Lithium, used to treat some mood disorders

-Metotrexate (cancer and immunosuppressive medication), used at high doses of 15mg/week

- Hidantoínas and phenytoin, used for epilepsy

-Sulfamethoxazole, used for bacterial infections

Associations that require caution:

-Inhibitors of the ECA, diuretics, and angiotensin II antagonists, used for high blood pressure and heart problems

-Pentoxifylline and oxpentifylline, used to treat chronic venous ulcers

-Zidovudine, used to treat viral infections

-Aminoglycoside antibiotics, used for bacterial infections

-Sulfonilureas (e.g. chlorpropamide and glibenclamide), used for diabetes

• Metotrexate, used at low doses, less than 15mg/week

Associations to be taken into account:

-Quinolones (e.g. ciprofloxacin, levofloxacin) used for bacterial infections

-Ciclosporina or tacrolimus, used to treat immune system diseases and organ transplants

-Streptokinase and other thrombolytic and fibrinolytic medications; that is, medications used to break down blood clots

-Probenecid, used for gout

-Digoxin, used in the treatment of chronic heart failure

-Mifepristone, used for abortion

-Antidepressants of the ISRS type (Selective Serotonin Reuptake Inhibitors)

-Antiplatelet agents used to reduce platelet aggregation and blood clot formation.

• Beta-blockers, used for high blood pressure and heart problems
• Tenofovir, deferasirox, pemetrexed.

If you have any doubts about taking other medications with Enantyum, consult your doctor or pharmacist.

Pregnancy, Lactation, and Fertility

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Do not use Enantyum during the last three months of pregnancy or while breastfeeding. It may cause kidney and heart problems in your fetus. It may affect your predisposition and that of your baby to bleed and delay or prolong delivery more than expected.

Do not take Enantyum during the first six months of pregnancy unless it is clearly necessary and as indicated by your doctor. If you need treatment during this period or while trying to become pregnant, you should take the minimum dose for the shortest possible time.

From week 20 of pregnancy, Enantyum may cause kidney problems in your fetus if taken for more than a few days, which may cause low amniotic fluid levels surrounding the baby (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the baby's heart. If you need treatment for more than a few days, your doctor may recommend additional monitoring.

Enantyum is not recommended for use while trying to conceive or while studying a fertility problem.

Regarding potential effects on female fertility, see also section 2, "Warnings and Precautions".

Driving and Operating Machines

Enantyum may slightly affect your ability to use machines and drive, as it may cause drowsiness or dizziness. If you notice these effects, do not use machines or drive until these symptoms disappear. Consult your doctor.

Enantyum contains ethanol and sodium

This medication contains up to 200 mg of alcohol (ethanol) in each 2 ml ampoule, equivalent to 3 mg/kg/dose (10% v/v). The amount in a 2 ml ampoule of this medication is equivalent to less than 5 ml of beer or 2 ml of wine.

The small amount of alcohol in this medication does not produce any perceptible effect.

This medication contains less than 1 mmol of sodium (23 mg) per dose; that is, it is essentially "sodium-free".

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The effective dose should be used for the shortest time necessary to relieve symptoms. If you have an infection, consult a doctor immediately if symptoms (such as fever and pain) persist or worsen (see section 2).

Your doctor will tell you the dose of Enantyum you need, according to the type, severity, and duration of your symptoms. The recommended dose is generally 1 ampoule (50 mg) every 8 – 12 hours. If necessary, a second ampoule may be administered 6 hours after the first administration. In no case should the maximum daily dose of 150 mg of Enantyum (3 ampoules) be exceeded.

Do not use Enantyum for more than two days. Switch to an oral analgesic when possible.

Patients with advanced age and decreased renal function, as well as patients with kidney or liver dysfunction, should not exceed a total daily dose of 50 mg of Enantyum (1 ampoule).

Form of use and administration routes

Enantyum can be administered via intramuscular or intravenous routes (the technical details for intravenous administration are described in section 7).

When administered via intramuscular injection, the solution should be injected immediately after extraction from the amber-colored injection ampoule by slow and deep injection into the muscle.

It should only be used if the solution is transparent and colorless.

Use in children and adolescents

This medication should not be used in children and adolescents (under 18 years old).

If you use more Enantyumthan you should

If you have taken too much medication, immediately inform your doctor or pharmacist or go to the emergency service of your nearest hospital or call the Toxicological Information Service, phone: 91.562.04.20, indicating the medication and the amount taken. Please remember to always carry the medication packaging or this leaflet with you.

If you forgot to use Enantyum

Do not use a double dose to compensate for the missed doses. Use the next dose when due (according to section 3 “How to use Enantyum”).

If you have any doubts about the use of this medication, consult your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The possible side effects are listed below in order of frequency.

Frequent side effects (may affect up to 1 in 10 people):

Nausea and/or vomiting and pain at the injection site, reactions at the injection site, including inflammation, hematoma, or hemorrhage.

Less frequent side effects (may affect up to 1 in 100 people):

Bloody vomiting, low blood pressure, fever, blurred vision, dizziness, drowsiness, sleep disorders, headache, anemia, abdominal pain, constipation, heavy digestion, diarrhea, dry mouth, hot flashes, skin rash, dermatitis, itching, increased sweating, fatigue, pain, feeling cold.

Rare side effects (may affect up to 1 in 1,000 people):

Peptic ulcer, bleeding peptic ulcer, or perforated peptic ulcer, high blood pressure, fainting, slow breathing, superficial vein inflammation due to blood clot (superficial thrombophlebitis), isolated heart palpitations (extrasystole), increased heart rate, peripheral edema, laryngeal edema, loss of appetite (anorexia), abnormal sensation, feverish sensation, and chills, ringing in the ears (tinnitus), pruritic skin rash, jaundice, acne, lower back pain, renal pain, frequent urination, menstrual irregularities, prostate irregularities, muscle stiffness, joint stiffness, muscle cramps, abnormal liver tests (blood test), increased blood glucose (hyperglycemia), decreased blood glucose (hypoglycemia), increased triglycerides in the blood (hypertriglyceridemia), ketones in the urine (ketonuria), protein in the urine (proteinuria), liver cell damage (hepatitis), acute renal insufficiency.

Very rare side effects (may affect up to 1 in 10,000 people):

Anaphylactic reaction (hypersensitivity reaction that can also lead to collapse), skin ulcers, mouth, eye, and genital area (Stevens-Johnson syndrome, Lyell syndrome), facial swelling, lip and throat swelling (angioedema), difficulty breathing due to contraction of respiratory tract muscles (bronchospasm), difficulty breathing, pancreatitis, skin sensitivity and hypersensitivity reactions to light exposure, kidney damage, decreased white blood cell count (neutropenia), decreased platelet count (thrombocytopenia).

Inform your doctor immediately if you notice any digestive side effects at the beginning of treatment (e.g. stomach pain or burning or bleeding) or if you have previously experienced any of these side effects due to prolonged treatment with anti-inflammatory drugs. All of the above is especially important if you are elderly.

Stop taking Enantyum as soon as you detect the appearance of skin rash or any mucous membrane lesions (e.g. inside the mouth) or any sign of allergy.

During treatment with non-steroidal anti-inflammatory drugs, cases of fluid retention and swelling (especially in ankles and legs), increased blood pressure, and heart failure have been reported.

Medicines like Enantyum may be associated with a small increased risk of suffering a heart attack ("myocardial infarction") or a stroke ("cerebral infarction").

In patients with systemic lupus erythematosus or mixed connective tissue disease, anti-inflammatory drugs may exceptionally cause isolated cases of fever, headache, and neck stiffness.

The most commonly observed side effects are of a gastrointestinal nature. They may cause peptic ulcers, perforation, or gastrointestinal bleeding, sometimes fatal, especially in elderly patients.

After administration, nausea, vomiting, diarrhea, flatulence, constipation, indigestion, abdominal pain, melena, hematemesis, ulcerative stomatitis, worsening of colitis, and Crohn's disease have been reported. Less frequently, gastric wall inflammation (gastritis) has been observed.

Like other NSAIDs, hematological reactions (purpura, aplastic and hemolytic anemia, and more rarely agranulocytosis and medullary hypoplasia) may appear.

Inform your doctor immediately if signs of infection appear or worsen while using Enantyum.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and on the ampule. The expiration date is the last day of the month indicated.

Conserve the ampule in the original packaging to protect it from light.

Do not use this medication if you observe that the solution is not transparent or colorless, or if it shows other signs of deterioration (e.g. particles). Enantyum injectable and infusion solution is indicated for use as a single-dose preparation and should be injected immediately after extraction from the topaz ampule. Unused solution should be discarded (see the following section “Disposal”).

Medications should not be thrown away through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Enantyum

• The active ingredient is dexketoprofen (as dexketoprofen trometamol). Each ampoule contains 50 mg of dexketoprofen.
• The other components are alcohol (ethanol, see section 2, Enantyum contains ethanol), sodium chloride, sodium hydroxide, and water for injection.

Appearance of the product and contents of the package:

Enantyum is presented in the form of injectable and infusion solution.

It is presented in containers that contain 1, 5, 6, 10, 20, 50, and 100 glass ampoules of Type I topaz with 2 ml of transparent and colorless solution.

Only some package sizes may be marketed.

Marketing Authorization Holder

Laboratorios Menarini, S.A.

Alfons XII, 587 - Badalona (Barcelona) Spain

Responsible for manufacturing

Alfasigma S.p.A.

Via Enrico Fermi, 1

65020 Alanno (Pescara)

Italy

or

A. Menarini Manufacturing Logistics and Services, s.r.l.

Via Sette Santi n.3 – Florence – Italy

or

Zambon S.p.A.

via della Chimica, 9

36100 Vicenza

Italy

This medicinal product is authorized in the member states of the European Economic Area with the following names:

Spain (EMR), Italy: Enantyum

Latvia: Ketesse

Greece: Viaxal

Date of the last review of this leaflet:

Other sources of information

The detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

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