KETESSE 50 mg/2 ml Injectable Solution and Perfusion Solution

2. What you need to know before you use Ketesse

Do not use Ketesse:

• 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 previous 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 Ketesse:

• 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 medicines that increase the risk of gastrointestinal ulcers or bleeding, such as oral corticosteroids, some antidepressants (of the SSRI type: Selective Serotonin Reuptake Inhibitors), agents that prevent blood clot formation such as acetylsalicylic acid or anticoagulants such as warfarin. In these cases, consult your doctor before taking Ketesse: your doctor may prescribe an additional medicine to protect your stomach (e.g. misoprostol or other medicines 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 disorders (e.g. you have high blood pressure, suffer from diabetes, have high cholesterol, or are a smoker). You should consult your treatment with your doctor or pharmacist. Medicines like Ketesse may be associated with a small increased risk of heart attacks ("myocardial infarction") or strokes ("cerebrovascular accident"). 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 suffer from 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 (Ketesse may reduce your fertility, so you should not use it if you are planning to become pregnant or if you are undergoing fertility studies);
• If you are in the first or second trimester of pregnancy;
• If you have a blood disorder or blood cell disorder;
• If you have systemic lupus erythematosus or mixed connective tissue disease (immune system diseases that affect connective tissue);
• If you have an infection; see the "Infections" heading below;
• If you have asthma, combined with chronic rhinitis or sinusitis, and/or nasal polyps, you are at greater risk of being allergic to acetylsalicylic acid and/or NSAIDs than the rest of the population. The administration of this medicine may cause asthma attacks or bronchospasm, particularly in patients allergic to acetylsalicylic acid or NSAIDs.

Infections

Ketesse may mask the signs of an infection, such as fever and pain. Consequently, Ketesse 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 are taking this medicine 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 medicine.

Children and adolescents

Ketesse 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 Ketesse 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 change if taken together.

It is especially important that you always inform your doctor, dentist or pharmacist if, in addition to Ketesse, 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 medicines used to prevent blood clot formation
• Lithium, used to treat some mood disorders
• Methotrexate (cancer and immunosuppressive medicine), used at high doses of 15mg/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 to treat bacterial infections
• Sulfonylureas (e.g. chlorpropamide and glibenclamide), used for diabetes
  • Methotrexate, used at low doses, less than 15mg/week

Combinations to be taken into account:

• Quinolones (e.g. ciprofloxacin, levofloxacin) used for bacterial infections
• Ciclosporin or tacrolimus, used to treat immune system diseases and organ transplants
• Streptokinase and other thrombolytic and fibrinolytic medicines; i.e. medicines 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.
  • Betablockers, used for high blood pressure and heart disorders
  • Tenofovir, deferasirox, pemetrexed.

If you have any doubts about taking other medicines with Ketesse, 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 using this medicine.

Do not use Ketesse during the last three months of pregnancy or if you are breastfeeding. It may cause kidney and heart problems in your fetus. It may affect your and your baby's ability to bleed and prolong or prolong labor more than expected.

You should not take Ketesse 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 the 20th week of pregnancy, Ketesse may cause kidney problems in your fetus if taken for more than a few days, which may cause 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 checks.

The use of Ketesse is not recommended while trying to conceive or while studying a fertility problem.

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

Driving and using machines

Ketesse 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 disappear. Ask your doctor for advice.

Ketesse 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 Ketesse

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

The effective lowest dose should be used during the shortest time necessary to relieve the 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 Ketesse 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 administration of the first. In no case should the maximum daily dose of 150 mg of Ketesse (3 ampoules) be exceeded.

Do not use Ketesse for more than two days. Switch to an oral pain reliever when possible.

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

Method of use and administration routes

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

When Ketesse 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 of age).

If you use more Ketesse 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, telephone: 91.562.04.20, indicating the medicine and the amount taken. Please remember to always carry the medicine package or this leaflet with you.

If you forget to use Ketesse:

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

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, 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, slow 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 triglycerides in blood (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), breathing difficulties, pancreatitis, skin sensitivity and hypersensitivity reactions to light, kidney damage, decreased number of white blood cells (neutropenia), decreased number of platelets (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 non-steroidal anti-inflammatory drugs. All of the above is especially important if you are elderly.

Stop taking Ketesse 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 Ketesse 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, gastric wall inflammation (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 Ketesse.

Reporting of 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 Ketesse

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). Ketesse injectable solution and for perfusion is indicated for use as a single-dose preparation and must 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 that 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 that you no longer need. This way, you will help protect the environment.

6. Packaging Content and Additional Information

Ketesse Composition

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

Product Appearance and Packaging Content:

Ketesse is presented in the form of an injectable solution and for perfusion.

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

Only some packaging sizes may be marketed.

Marketing Authorization Holder

MENARINI INTERNATIONAL O.L., S.A.

1, Avenue de la Gare, L-1611 Luxembourg

Local Representative:

GUIDOTTI FARMA, S.L.

Alfons XII, 587

08918 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 with the following names:

Spain (EMR), Belgium, Finland, France, Italy, Luxembourg, Portugal: Ketesse

Cyprus, Greece: Nosatel

Austria, Czech Republic: Dexoket

Estonia, Latvia, Lithuania: Dolmen

Germany: Sympal

Hungary: Ketodex forte

Ireland, Malta: Keral

Poland: Dexak

Slovakia: Dexadol

Slovenia: Menadex

Netherlands: Stadium

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 content of one ampoule (2 ml) of Ketesse must be diluted in a volume of 30 to 100 ml with saline solution, glucose solution, or Ringer lactate.

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

• Intravenous Bolus: if necessary, the content of one ampoule (2 ml) of Ketesse can be administered as a slow intravenous bolus, over a period of not less than 15 seconds.

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

Instructions for Proper Use

When administering Ketesse via intravenous bolus, the solution must be injected immediately after extraction from the topaz-colored ampoule.

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

Only transparent and colorless solution should be used.

Compatibilities

Ketesse 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.

Ketesse diluted in a volume of 100 mlof saline or glucose solution for perfusion 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 solutions of Ketesse have been stored in plastic bags or administration devices manufactured with Ethyl Vinyl Acetate (EVA), Cellulose Propionate (CP), Low-Density Polyethylene (LDPE), and Polyvinyl Chloride (PVC).