ARTROTEC 50 mg/200 micrograms FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

ARTROTEC50mg/200micrograms coated tablets

Diclofenac/Misoprostol

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

• Keep this leaflet, as 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, as it may harm them,

even if their symptoms are the same as yours.

• If you experience any side effects, talk to your doctor or pharmacist, even if it is not listed in this leaflet. See section 4.

Contents of the pack

1. What is Artrotec and what is it used for
2. What you need to know before you take Artrotec
3. How to take Artrotec
4. Possible side effects
5. Storage of Artrotec
6. Contents of the pack and further information

1. What is Artrotec and what is it used for

Artrotec is a medicine that combines two components: diclofenac and misoprostol. Diclofenac provides anti-inflammatory and analgesic properties, and misoprostol has a protective effect on the stomach and duodenal mucosa.

Artrotec is used for the treatment of rheumatoid arthritis and osteoarthritis in patients with a high risk of developing gastrointestinal lesions, either due to advanced age or a history of gastroduodenal ulcers.

2. What you need to know before you take Artrotec

Do not take Artrotec:

• if you are allergic to diclofenac or misoprostol, or to any of the other ingredients of this medicine (listed in section 6).
• if you are allergic (hypersensitive) to acetylsalicylic acid (aspirin), other prostaglandins, or other non-steroidal anti-inflammatory medicines.
• if you currently have an active stomach or duodenal ulcer, bleeding, or perforation.
• if you are pregnant, trying to become pregnant, or think you may be pregnant (see section "Pregnancy, breastfeeding, and fertility" and section 4. Possible side effects).
• if you have established heart disease and/or cerebrovascular disease, for example, if you have had a heart attack, stroke, mini-stroke (TIA), or blockages in the blood vessels of the heart or brain, or have undergone surgery to remove a blockage or perform a coronary bypass.
• if you are going to have heart surgery (bypass).
• if you have or have had problems with blood circulation (peripheral arterial disease).
• if you have severe kidney or liver failure.
• if you are a woman of childbearing age and are not using an effective contraceptive method to

avoid becoming pregnant (see section "Pregnancy" for more information).

Some people MUST NOT use Artrotec. Consult your doctor if:

• you think you may be allergic to diclofenac sodium, acetylsalicylic acid, ibuprofen, or any other ingredient of Artrotec (listed at the end of the leaflet). Signs of a hypersensitivity reaction are swelling of the face and mouth (angioedema), breathing difficulties, chest pain, runny nose, skin rash, or any other allergic reaction.

Warnings and precautions

It is important to use the smallest dose that relieves/control your pain and do not take this medicine, Artrotec, for longer than necessary to control your symptoms.

Tell your doctor if you have recently undergone or are going to undergo stomach or intestinal surgery before receiving/taking/using Artrotec, as Artrotec may worsen the healing of intestinal wounds after surgery.

Consult your doctor or pharmacist before starting to take Artrotec:

• If you have had or developed an ulcer, bleeding, or perforation in the stomach or duodenum, which may be manifested by severe and persistent abdominal pain and/or black stools, or even without prior warning symptoms.

This risk is higher when using high doses and prolonged treatments, in patients with a history of peptic ulcers, and in elderly patients.

• If during treatment with Artrotec, you develop an ulcer or bleeding in the stomach or duodenum, you must discontinue treatment and inform your doctor immediately.
• If you are an elderly patient, have cardiovascular disease, are being treated with acetylsalicylic acid, have or have had gastrointestinal disease, as you may be at higher risk of developing these gastrointestinal disorders.
• If you are pregnant or plan to become pregnant (see section "Pregnancy").

Due to the risk to the fetus, treatment with Artrotec should be discontinued immediately.

• If you are a woman of childbearing age (see also the section "Pregnancy"). It is essential to use

effective contraceptive methods while taking this medicine.

• Make sure your doctor knows before taking diclofenac:
• • if you smoke or consume alcohol
  • if you have diabetes
  • if you have angina, blood clots, high blood pressure, high cholesterol, or high triglycerides.
  • if you are taking medications that alter blood coagulation or increase the risk of ulcers, such as oral anticoagulants or antiplatelet agents of the acetylsalicylic acid type (aspirin). You should also discuss the use of other medications that may increase the risk of such bleeding, such as corticosteroids, selective serotonin reuptake inhibitors, and other non-steroidal anti-inflammatory drugs.
  • if you have Crohn's disease or ulcerative colitis, as medications like Artrotec may worsen these conditions.
• Cardiovascular precautions

Medicines like Artrotec may be associated with a moderate increase in the risk of suffering heart attacks ("myocardial infarction") or strokes that can be severe and even fatal, especially when used in high doses and prolonged treatments. Do not exceed the recommended dose or treatment duration.

If you have heart problems, a history of strokes, or think you may be at risk for these conditions (for example, you have high blood pressure, diabetes, high cholesterol, or are a smoker), you should consult your doctor or pharmacist about this treatment.

Similarly, this type of medication may cause fluid retention, especially in patients with heart failure and/or high blood pressure (hypertension). You should also be cautious if you are prone to fluid retention.

If your hypertension worsens or you develop high blood pressure during treatment with Artrotec, you should inform your doctor immediately.

• If during treatment, and particularly in the first few months, you experience skin rash, skin redness, and other symptoms of allergy. In this case, you should discontinue treatment and inform your doctor immediately.
• If you have ever had a severe skin rash or skin peeling, blisters, or sores in the mouth after taking Artrotec or other painkillers.
• If you have liver (liver failure), kidney (renal failure), or heart (heart failure) problems, inform your doctor before starting treatment, as closer monitoring will be necessary.
• If you are of childbearing age and do not use an effective contraceptive method. If you suspect pregnancy, you should stop treatment with Artrotec and inform your doctor immediately.

Side effects can be minimized by using the lowest effective dose for the shortest possible time.

Using Artrotec with other medicines

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription, including herbal remedies.

If Artrotec is taken with other medicines, it may alter their effect or increase their toxicity.

These include:

• acetylsalicylic acid and other non-steroidal anti-inflammatory medicines (for pain, fever, and inflammation)
• medicines to lower blood pressure (diuretics, ACE inhibitors, angiotensin II antagonists, beta blockers)
• lithium (medicine for mental disorders)
• digoxin (medicine to regulate heart rhythm)
• anticoagulants (medicines that alter blood coagulation)
• antidiabetics (medicines to control blood sugar)
• medicines that may increase the risk of bleeding or ulcers in the stomach or duodenum, such as antiplatelet agents, corticosteroids, and selective serotonin reuptake inhibitors
• methotrexate (medicine used in rheumatological diseases)
• cyclosporin, tacrolimus (medicines used in patients who have received a transplant)
• medicines that may delay the absorption of diclofenac, such as antacids, or increase the diarrhea associated with misoprostol, such as antacids containing magnesium
• potent CYP2C9 inhibitors such as sulfinpyrazone and voriconazole
• voriconazole (medicine to treat fungal infections)

Taking Artrotec with food and drinks

The tablet should be taken preferably after the main meals.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

Due to the possible risk of harm to the fetus, you should ensure that you are not pregnant before starting treatment.

Artrotec is contraindicated in pregnant women, as it can induce uterine contractions associated with abortion, loss of amniotic fluid, premature birth, birth defects, and fetal death. Therefore, pregnancy should be ruled out before starting treatment, and an adequate contraceptive method should be used during treatment.

Your doctor will inform you about the risks if you become pregnant while taking Artrotec, as it may cause spontaneous abortion, premature birth, or fetal malformation (congenital anomalies). NEVER take this medicine if you are pregnant, as it may also have serious consequences for your child, especially in the heart, lungs, and/or kidneys, including death. If you have received treatment with this medicine during pregnancy, consult your doctor. If you decide to continue with the pregnancy, close ultrasound monitoring of the pregnancy should be performed, paying special attention to the limbs and head.

For patients of childbearing age, it should be noted that medications like Artrotec have been associated with a decrease in fertility.

Breastfeeding

Ask your doctor or pharmacist for advice before taking this medicine if you are breastfeeding.

Artrotec should not be used if you are breastfeeding, as part of the medicine may pass into breast milk and cause unwanted effects in the baby, such as diarrhea.

Driving and using machines

The influence of Artrotec on the ability to drive and use machines is unknown, as no appropriate studies have been conducted.

Artrotec contains lactose, hydrogenated castor oil, and sodium

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

This medicine may cause stomach upset and diarrhea because it contains hydrogenated castor oil.

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially "sodium-free".

3. How to take Artrotec

Follow exactly the administration instructions of this medicine indicated by your doctor.

In case of doubt, consult your doctor or pharmacist again.

The tablet should be taken preferably after the main meals. The coated tablets should be swallowed whole, not chewed, broken, or dissolved.

Adults

The recommended dose is one coated tablet two or three times a day, according to medical criteria.

Elderly patients

No dose adjustment is necessary in this type of patient.

Patient with altered liver function or moderately altered kidney function

No dose adjustment is necessary in this type of patient, although it is recommended to start treatment with the lowest dose.

Use in children and adolescents

The efficacy and safety of the product have not been studied in children under 18 years of age.

If you take more Artrotec than you should

If you have accidentally taken too many tablets, consult your doctor immediately or the Toxicology Information Service. Telephone 91 562 04 20.

You may require medical attention. It is advisable to induce vomiting.

If you forget to take Artrotec

Do not take a double dose to make up for forgotten doses.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medications, this medication can produce adverse effects, although not all people suffer from them.

Gastrointestinal Effects

The most frequent adverse effects that occur with medications like Artrotec are gastrointestinal: peptic ulcers, perforation or gastrointestinal bleeding (in some cases fatal), especially in elderly patients (see also the section "Warnings and Precautions"). Nausea, vomiting, diarrhea, flatulence, constipation, heartburn, abdominal pain, blood in stool, vomiting blood, inflammation and ulcers in the mouth mucosa, worsening of ulcerative colitis and Crohn's disease (see also the section "Warnings and Precautions") have also been observed. Gastritis has been observed less frequently.

Abdominal pain and diarrhea appeared at the beginning of treatment, were generally transient and of mild to moderate intensity. Abdominal pain and diarrhea can be reduced by taking Artrotec with food and avoiding the use of antacids that contain magnesium.

Cardiovascular Effects

Medications like Artrotec may be associated with an increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Edema (fluid retention), arterial hypertension, and heart failure have also been observed in association with treatments with medications of the Artrotec type.

Cutaneous Effects

Medications like Artrotec may be associated, in very rare cases, with blistering reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

Severe allergic skin reaction, which can include large, generalized red or dark spots, skin swelling, blisters, and itching (generalized fixed drug eruption).

Hepatic Effects

Medications like Artrotec may be associated, frequently, with an increase in transaminases (SGPT, SGOT), blood enzymes that measure liver function.

Hepatitis with or without jaundice (rare) and fulminant hepatitis (isolated cases) have also been reported.

The frequency of appearance of adverse effects reported with Artrotec was:

Very Common Adverse Effects (may affect more than 1 in 10 patients):

• Abdominal pain, diarrhea, nausea, heartburn (dyspepsia).

Common Adverse Effects (may affect up to 1 in 10 patients):

• Insomnia.
• Headache, dizziness.
• Gastrointestinal ulcer, duodenal inflammation, stomach inflammation, esophageal inflammation, gastrointestinal inflammation, vomiting, constipation, flatulence, belching.
• Skin rash, itching.
• Fetal malformations.
• Alteration of some blood parameters that measure liver function [elevated alanine aminotransferase (ALT), decreased hematocrit, increased alkaline phosphatase (ALP)].
• Low red blood cell count in blood tests (decreased hematocrit).

Uncommon Adverse Effects (may affect between 1 and 10 in 1,000 patients):

• Vaginal infection.
• Decreased platelet count in the blood (thrombocytopenia).
• Stroke.
• Blurred vision.
• Myocardial infarction, heart failure.
• Arterial hypertension.
• Difficulty breathing (dyspnea).
• Gastrointestinal bleeding, mouth mucosa inflammation (stomatitis).
• Red, raised, and itchy skin lesions (urticaria), purple spots on the skin and mucous membranes (purpura).
• Intermenstrual bleeding (metrorrhagia), excessive or prolonged menstruation (menorrhagia), vaginal bleeding (which may occur after menopause), menstrual disorders.
• Fever, swelling (edema), chills.
• Increased aspartate aminotransferase (AST), a blood enzyme that measures liver function.

Rare Adverse Effects (may affect between 1 and 10 in 10,000 patients):

• Severe allergic reaction (anaphylactic reaction).
• Nightmares.
• Pancreatitis.
• Hepatitis with or without jaundice.
• Skin rash with blister formation (bullous dermatitis), severe swelling under the skin (angioedema).
• Breast pain, painful menstruation (dysmenorrhea).

Very Rare Adverse Effects (may affect less than 1 in 10,000 patients)

• Severe blistering reactions on the skin (Stevens-Johnson syndrome) and toxic epidermal necrolysis (TEN).

Adverse Effects of Unknown Frequency (cannot be estimated from available data):

• Hemolytic anemia, decrease in a type of blood cells called neutrophils (agranulocytosis), inhibition of platelet aggregation.
• Fluid retention.
• Mood changes.
• Aseptic meningitis (characterized by headache, fever, and inflammation of the brain lining).
• Kounis syndrome.
• Vasculitis.
• Gastrointestinal perforation.
• Severe liver dysfunction (liver failure), yellowing of the skin or whites of the eyes (jaundice), liver inflammation with fatal outcome (fulminant hepatitis).
• Skin and mucous membrane disease with blisters and lesions (erythema multiforme), skin inflammation with scaling (exfoliative dermatitis), skin and mucous membrane reactions, DRESS syndrome.
• Allergic skin reaction, which can include round or oval red spots, skin swelling, blisters, and itching (fixed drug eruption). It can also cause skin darkening in the affected areas, which may persist after healing. Fixed drug eruption usually reappears in the same or same areas if the medication is taken again.
• Severe kidney dysfunction (renal failure), kidney alteration, renal papillary necrosis, nephrotic syndrome, interstitial nephritis, membranous glomerulonephritis, minimal lesion glomerulonephritis, glomerulonephritis.
• Fetal death, amniotic fluid passage into the mother's bloodstream, which can cause heart failure (anaphylactoid syndrome of pregnancy), incomplete abortion, premature birth, abnormal uterine contractions, placental retention in the uterus after delivery.
• Abnormal uterine bleeding, uterine cramps, female infertility (reduced female fertility).
• Uterine rupture or perforation.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is an 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 medication.

5. Storage of Artrotec

Keep this medication out of sight and reach of children.

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

Do not store at a temperature above 25°C.

Store in the original packaging. Do not use Artrotec if you observe that the packaging is damaged or open.

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

6. Package Contents and Additional Information

Composition of Artrotec

• The active ingredients are: diclofenac sodium and misoprostol.
• The other components (excipients) are lactose monohydrate, microcrystalline cellulose, gluten-free cornstarch, povidone, magnesium stearate, methacrylic acid copolymer type C, sodium hydroxide, talc, triethyl citrate, crospovidone, anhydrous colloidal silica, and hydrogenated castor oil.

Appearance of the Product and Package Contents

Artrotec is presented in biconvex, round, white film-coated tablets, with an approximate diameter of 10-11 mm and marked with " " on one side and "Searle 1411" on the other.

Artrotec is presented in cold-formed aluminum blisters, containing 40 film-coated tablets per package.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Pfizer, S.L.

Avda. de Europa, 20-B

Parque Empresarial La Moraleja,

28108 Alcobendas (Madrid).

Manufacturer:

Piramal Pharma Solutions (Dutch) B.V.

Level, 7e verdieping

Bargelaan 200

2333 CW

Leiden

Netherlands

Date of the Last Revision of this Prospectus: September 2025

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