ENANTYUM 50 mg/2 ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Enantyum 50 mg/2 ml solution for injection and infusion

dexketoprofen

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is Enantyum and what is it used for.
2. What you need to know before you use Enantyum.
3. How to use Enantyum,
4. Possible side effects.
5. Storing Enantyum.

1. Contents of the pack and other information.

1. What is Enantyum and what is it used for

Enantyum is a pain reliever belonging to the family of non-steroidal anti-inflammatory drugs (NSAIDs).

It is indicated for the symptomatic treatment of moderate to severe acute pain such as post-operative pain, renal colic (severe pain in the kidney) and lumbar pain (lumbago), when oral administration is not appropriate.

2. What you need to know before you use Enantyum:

Do not use Enantyum:

• If you are allergic to dexketoprofen or any of the other ingredients of this medicine (listed in section 6);
• If you are allergic to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs;
• If you have asthma or have suffered from asthma attacks, acute rhinitis (a short period of inflammation of the nasal mucosa), nasal polyps (fleshy growths in the nasal passages due to allergy), urticaria (skin rash), 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 other non-steroidal anti-inflammatory drugs;
• If you have suffered from photoallergic or phototoxic reactions (a special form of redness or sunburn) while taking ketoprofen (a non-steroidal anti-inflammatory drug) or fibrates (medicines used to reduce blood fat levels);
• If you have a peptic ulcer, stomach or intestinal bleeding, or if you have had a history of bleeding, ulceration, or perforation of the stomach or intestine;
• If you have digestive problems (e.g., indigestion, heartburn)
• If you have had bleeding or perforation of the stomach or duodenum due to the use of a non-steroidal 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 impairment, or severe hepatic impairment;
• If you have bleeding disorders or blood coagulation disorders;
• If you are severely dehydrated (have lost a lot of body fluid) due to vomiting, diarrhea, or insufficient fluid intake;
• If you 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 a history of chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease);
• If you have had stomach or intestinal problems in the past;
• If you are taking medications that increase the risk of gastrointestinal ulcers or bleeding, such as oral corticosteroids, some antidepressants (e.g., selective serotonin reuptake inhibitors), 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, or think you may be at risk for these disorders (e.g., you have high blood pressure, diabetes, high cholesterol, or are a smoker). You should consult your treatment with your doctor or pharmacist. Medications like Enantyum may be associated with a small increased risk of heart attacks or strokes. This risk is higher when high doses and prolonged treatments are used. Do not exceed the recommended dose or duration of treatment;
• If you are an elderly patient, as you may experience a higher incidence of adverse effects (see section 4). If these occur, consult your doctor immediately;
• If you have any allergies or have had allergy problems in the past;
• If you have kidney, liver, or heart disease (hypertension and/or heart failure), fluid retention, or have had these problems in the past;
• If you are taking diuretics or have dehydration and reduced blood volume due to excessive fluid loss (e.g., due to excessive urination, diarrhea, or vomiting);
• If you are a woman with fertility problems (Enantyum may reduce your fertility, so you should not use it if you are planning to become pregnant or are undergoing fertility studies);
• If you are in the first or second trimester of pregnancy;
• If you have a blood disorder or a disorder of 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" section below;
• If you have asthma, combined with chronic rhinitis or sinusitis, and/or nasal polyps, you are at a higher risk of being allergic to acetylsalicylic acid and/or NSAIDs than the rest of the 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. Consequently, Enantyum may delay the appropriate treatment of the infection, which may increase the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections related to chickenpox. If you take this medication while you have an infection and the symptoms of the infection 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 and adolescents. Therefore, safety and efficacy have not been established, and the product should not be used in children and adolescents.

Using Enantyum with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription. Some medicines must not be taken together. Others may need a dose adjustment if taken together.

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

Not recommended combinations:

• Acetylsalicylic acid, corticosteroids, and other non-steroidal anti-inflammatory drugs
• Warfarin, heparin, and other medications used to prevent blood clots
• Lithium, used to treat some mood disorders
• Methotrexate (cancer and immunosuppressive medication), used at high doses of 15 mg/week
• Hydantoins and phenytoin, used for epilepsy
• Sulfamethoxazole, used for bacterial infections

Combinations that require caution:

• ACE inhibitors, diuretics, and angiotensin II antagonists, used for high blood pressure and heart disorders
• Pentoxifylline and oxpentifylline, used to treat chronic venous ulcers
• Zidovudine, used to treat viral infections
• Aminoglycoside antibiotics, used for bacterial infections
• Sulfonylureas (e.g., chlorpropamide and glibenclamide), used for diabetes
  • Methotrexate, used at low doses, less than 15 mg/week

Combinations to be taken into account:

• Quinolones (e.g., ciprofloxacin, levofloxacin), used for bacterial infections
• Cyclosporin or tacrolimus, used to treat immune system diseases and organ transplants
• Streptokinase and other thrombolytic and fibrinolytic medications; i.e., medications used to dissolve blood clots
• Probenecid, used for gout
• Digoxin, used in the treatment of chronic heart failure
• Mifepristone, used for abortion
• Antidepressants of the SSRI 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 disorders
  • Tenofovir, deferasirox, pemetrexed.

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

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

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 and your baby's ability to clot and prolong labor more than expected.

You should not take Enantyum during the first six months of pregnancy unless clearly necessary and as directed 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 the 20th week of pregnancy, Enantyum may cause kidney problems in your fetus if taken for more than a few days, which may lead to low levels of amniotic fluid 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.

The use of Enantyum is not recommended 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 using 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 they have resolved. Ask your doctor for advice.

Enantyum contains ethanol and sodium

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

The small amount of alcohol in this medicine does not produce any noticeable effect.

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

3. How to use Enantyum

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The lowest effective dose should be used for the shortest duration necessary to relieve symptoms. If you have an infection, consult a doctor without delay if the symptoms (such as fever and pain) persist or worsen (see section 2).

Your doctor will indicate 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 can be administered 6 hours after the administration of the first. 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.

Elderly patients with reduced renal function and patients with kidney or liver dysfunction should not exceed the total daily dose of 50 mg of Enantyum (1 ampoule).

Method of use and administration routes

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

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

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

Use in children and adolescents

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

If you use more Enantyum than you should

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

If you forget to use Enantyum

Do not use a double dose to make up for forgotten doses. Use the next dose when scheduled (according to section 3 "How to use Enantyum").

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

4. Possible Adverse Effects

Like all medicines, this medicine may cause adverse effects, although not all people suffer from them.

Possible adverse effects are detailed below according to their frequency.

Frequent Adverse 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 bleeding.

Uncommon Adverse Effects (may affect up to 1 in 100 people):

Vomiting blood, 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 of cold.

Rare Adverse Effects (may affect up to 1 in 1,000 people):

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

Very Rare Adverse Effects (may affect up to 1 in 10,000 people):

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

Inform your doctor immediately if you notice any adverse effect of a digestive type at the start of treatment (e.g., stomach pain or burning or bleeding) or if you have previously suffered from any of these adverse 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 a skin rash or any mucosal lesion (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 ("stroke").

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 adverse effects are of a gastrointestinal type. Peptic ulcers, perforation, or gastrointestinal bleeding may occur, sometimes fatal, especially in elderly patients.

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

As with other NSAIDs, hematological reactions (purpura, aplastic anemia, and hemolytic anemia, and more rarely agranulocytosis and bone marrow hypoplasia) may appear.

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

Reporting Adverse Effects

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

5. Conservation of Enantyum

Keep this medicine out of sight and reach of children.

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

Keep the ampoule in the original packaging to protect it from light.

Do not use this medicine 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 intended for use as a single-dose preparation and should be injected immediately after extraction from the topaz ampoule. The unused solution must be discarded (see the following section "elimination").

Medicines should not be thrown away through the sewers or in the trash. Deposit the packaging and medicines you no longer need in the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

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.

Product Appearance and Package Contents:

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

It is presented in packages containing 1, 5, 6, 10, 20, 50, and 100 topaz glass ampoules with 2 ml of transparent and colorless solution.

Only some package sizes may be commercialized.

Marketing Authorization Holder

LABORATORIOS MENARINI, S.A.

Alfons XII, 587 - Badalona (Barcelona) Spain

Manufacturer

Alfasigma S.p.A.

Via Enrico Fermi, 1

65020 Alanno (Pescara)

Italy

or

• 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 medicine is authorized in the member states of the European Economic Area under the following names:

Spain (EMR), Italy: Enantyum

Latvia: Ketesse

Greece: Viaxal

Date of the last revision of this prospectus:

Other Sources of Information

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

1. Information for Healthcare Professionals

This information is intended only for healthcare professionals:

Intravenous Use:

-Intravenous Infusion: the contents of an ampoule (2 ml) of Enantyum should be diluted in a volume of 30 to 100 ml with saline solution, glucose solution, or Ringer lactate.

The diluted solution should be administered by slow intravenous infusion over 10-30 minutes. The solution must always be protected from natural light.

-Intravenous Bolus: if necessary, the contents of an ampoule (2 ml) of Enantyum can be administered as a slow intravenous bolus, over a period of no less than 15 seconds.

Enantyum is contraindicated for intrathecal or epidural administration due to its ethanol content.

Instructions for Proper Use.When Enantyum is administered via intravenous bolus, the solution should be injected immediately after extraction from the topaz ampoule.

For administration as an intravenous infusion, the solution should be diluted aseptically and protected from natural light.

Only a transparent and colorless solution should be used.

Compatibilities

Enantyum has been shown to be compatible when mixed in small volumes(e.g., in a syringe) with injectable solutions of heparin, lidocaine, morphine, and theophylline.

The correctly diluted injectable solution is transparent.

Enantyum diluted in a volume of 100 mlof saline or glucose solution for infusion is compatible with the following injectable solutions: dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine, and theophylline.

No adsorption of the active ingredient has been observed when diluted Enantyum solutions have been stored in plastic bags or administration devices made of Ethyl Vinyl Acetate (EVA), Cellulose Propionate (CP), Low-Density Polyethylene (LDPE), and Polyvinyl Chloride (PVC).

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