Patient Information Leaflet

ARTROTEC50mg /200microgram coated tablets

Diclofenaco/Misoprostol

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others,

even if they have the same symptoms as you, as it may harm them.

• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Artrotec is a medication that combines two components: diclofenac and misoprostol. Diclofenac provides properties to combat inflammation (anti-inflammatory) and suppress painful sensations (analgesic), and misoprostol exerts a protective action on the stomach mucosa and duodenum.

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

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), to other prostaglandins or to other non-steroidal anti-inflammatory drugs.
• if you currently have an ulcer, bleeding or perforation of the stomach or duodenum.
• if you are pregnant, if you are trying to become pregnant or if you think you may be pregnant (see sectionPregnancy, breastfeeding and fertilityand 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 a procedure to remove an obstruction or bypass the coronary artery.
• if you are to undergo heart surgery (bypass).
• if you have or have had problems with blood circulation (peripheral arterial disease).
• if you have severe renal and hepatic insufficiency.
• if you are a fertile woman and are not using an effective contraceptive method to

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

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

• you think you may be allergic to diclofenac sodium, acetylsalicylic acid, ibuprofen or any other NSAID, or to any of the other ingredients of Artrotec (listed at the end of the leaflet). The 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 essential to use the smallest dose that relieves/controls pain and not to take this medicine, Artrotec, for longer than necessary to control your symptoms.

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

Consult your doctor or pharmacist before starting to take Artrotec:

• if you have had or develop an ulcer, bleeding or perforation in the stomach or duodenum, which may manifest by intense or persistent abdominal pain and/or by black stools, or even without previous warning symptoms.

This risk is greater when high doses and prolonged treatments are used, in patients with a history of peptic ulcer and in elderly patients.

• if during treatment with Artrotec, you develop an ulcer or bleeding in the stomach or duodenum,you must interrupt treatment and immediately inform your doctor
• if you are an elderly patient, have some type of cardiovascular disease, are being treated with acetylsalicylic acid, have or have had some type of gastrointestinal disease, as you may be at greater risk of developing this type of gastrointestinal alteration.
• if you are pregnant or intend to become pregnant (see section «Pregnancy»).

Due to the risk to the fetus, treatment with Artrotec must be interrupted immediately.

• if you are a fertile woman (see also the section «Pregnancy»). It is essential to use

effective contraceptive methods while taking this medicine.

• Ensure before taking diclofenac that your doctor knows:
• • 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 simultaneously medications that alter blood coagulation or increase the risk of ulcers, such as oral anticoagulants, or antiplatelet agents of the type of acetylsalicylic acid (aspirin). You must also inform them of the use of other medications that may increase the risk of such bleeding, such as corticosteroids, antidepressants that inhibit serotonin reuptake and other non-steroidal anti-inflammatory drugs.
  • if you have Crohn's disease or ulcerative colitis, as the type of medications such as Artrotec may worsen these pathologies.
• 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, suffer from diabetes, have high cholesterol, or are a smoker) you must consult this treatment with your doctor or pharmacist.

Similarly, this type of medication may cause fluid retention, especially in patients with heart failure and/or high blood pressure (hypertension). In the same way, you must be careful if you are a person prone to fluid retention.

if during treatment with Artrotec, your blood pressure worsens or you begin to have high blood pressure (hypertension) you mustimmediately inform your doctor.

• if during treatment, and particularly in the first few months, you present a skin rash, redness of the skin and other symptoms of allergy. In this case, you must interrupt treatment and immediately inform your doctor.
• if you have liver (hepatic insufficiency), kidney (renal insufficiency) or heart (cardiac insufficiency) problems inform your doctor before starting treatment, as you will need to be closely monitored.
• ifyou are fertile and do not use an effective contraceptive method.if you suspect the possibility of pregnancy, treatment with Artrotec must be suspended and you must immediately inform your doctor.

The side effects can be minimized by using the most effective dose for the shortest possible period.

Use of Artrotec with other medicines

Inform your doctor or pharmacist if you are using or have recently used other medicines, including over-the-counter medications and herbal remedies.

if Artrotec is taken with other medicines, it may modify its effect or increase its toxicity.

These include:

• acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (to treat pain, fever and inflammation)
• blood pressure-lowering medications (diuretics, ACE inhibitors, angiotensin II antagonists, beta-blockers)
• lithium (medication for mental disorders)
• digoxin (medication to regulate heart rhythm)
• anticoagulants (medications that alter blood coagulation)
• antidiabetic medications (medications to control blood sugar)
• medications that may increase the risk of bleeding or ulcers in the stomach or duodenum, such as antiplatelet agents, corticosteroids and antidepressants that inhibit serotonin reuptake
• methotrexate (medication used in rheumatological diseases)
• ciclosporin, tacrolimus (medications used in patients who have received a transplant)
• medications 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 sulfinpirazona and voriconazol
• voriconazol (medication for fungal infections)

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 intend to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

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

Artrotec is contraindicated in pregnant women as it induces uterine contractions associated with abortions, loss of amniotic fluid, premature births, congenital defects and fetal death. Therefore, you must rule out pregnancy before starting to use this medicine and use an appropriate contraceptive method during treatment with it.

Your doctor will inform you about the risks if you become pregnant while takingArtrotec, as it may cause spontaneous abortion, premature birth or abnormal fetal development (congenital anomalies). NEVER take this medicine if you are pregnant, as it may also have severe 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, a close follow-up of the pregnancy should be carried out, paying special attention to the limbs and head.

For fertile women, it should be taken into account that the type of medications such as Artrotec have been associated with a decrease in the ability to conceive.

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 the milk and cause undesirable effects in the baby, such as diarrhea.

Driving and operating machinery

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

Artrotec contains lactose, hydrogenated ricin oil and sodium

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

This medicine may cause stomach discomfort and diarrhea because it contains hydrogenated ricin oil.

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

Follow exactly the administration instructions for this medication as indicated by your doctor.

If in doubt, consult your doctor or pharmacist again.

The tablet should be taken preferably after 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, as determined by your doctor.

Senior patients

No dose adjustment is necessary for this type of patient.

Patients with altered liver function or moderately altered renal function

No dose adjustment is necessary for 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.

If you take more Artrotec than you should

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

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

If you forgot to take Artrotec

Do not take a double dose to compensate for the missed doses.

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

Like all medications, this medication may cause side effects, although not everyone will experience them.

Gastrointestinal side effects

The most common side effects that occur with medications like Artrotec are gastrointestinal: peptic ulcers, gastrointestinal perforation or hemorrhage (in some cases fatal), especially in elderly patients (see also the section "Warnings and precautions"). Nausea, vomiting, diarrhea, flatulence, constipation, heartburn, abdominal pain, bloody stools, vomiting with blood, inflammation, and mouth ulcers have also been observed. In addition, worsening of ulcerative colitis and Crohn's disease has been reported (see also the section "Warnings and precautions"). Less frequently, gastritis has been observed.

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 containing magnesium.

CARDIOVASCULAR SIDE EFFECTS

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

CUTANEOUS SIDE EFFECTS

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

HEPATIC SIDE EFFECTS

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

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

The frequency of reported side effects with Artrotec was:

Very common side effects (may affect more than 1 in 10 patients):

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

Common side effects (may affect up to 1 in 10 patients):

• Insomnia.
• Headache, dizziness.
• Gastrointestinal ulcers, duodenal inflammation, gastric 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).

Rare side 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.
• Hypertension.
• Dyspnea (difficulty breathing).
• Gastrointestinal hemorrhage, mouth mucosa inflammation (stomatitis).
• Rash, elevated, itchy, and red skin lesions (urticaria), purple skin and mucous membrane spots (purpura).
• Menstrual bleeding, excessive or prolonged menstruation (menorrhagia), vaginal bleeding (which may occur after menopause), menstrual irregularities.
• Fever, edema, chills.
• Increased aspartate aminotransferase (AST), a blood enzyme that measures liver function.

Rare side effects (may affect between 1 and 10 in 10,000 patients):

• Severe allergic reaction (anaphylactic reaction).
• Nightmares.
• Pancreatitis.
• Inflammation of the liver with or without yellowing of the skin (hepatitis with or without jaundice).
• Skin eruption with blister formation (dermatitis bullosa), severe subcutaneous edema.
• Mastalgia, dysmenorrhea.

Very rare side effects (may affect fewer than 1 in 10,000 patients)

• Very severe vesiculobullous skin reactions (Stevens-Johnson syndrome) and toxic epidermal necrolysis (NET).

Side effects of unknown frequency (cannot be estimated from available data):

• Hemolytic anemia, decreased neutrophil count (agranulocytosis), inhibition of platelet aggregation.
• Fluid retention.
• Mood changes.
• Asymptomatic meningitis (disease characterized by headache, fever, and inflammation of the brain's meninges).
• Kounis syndrome.
• Vasculitis (inflammation of blood vessels).
• Gastrointestinal perforation.
• Severe liver dysfunction (hepatic insufficiency), yellowing of the skin or eyes (jaundice), liver inflammation with fatal outcome (fulminant hepatitis).
• Skin and mucous membrane disease with blisters and lesions (erythema multiforme), skin inflammation with peeling (dermatitis exfoliativa), skin and mucous membrane reactions, DRESS syndrome.
• Severe kidney dysfunction (renal failure), kidney alteration, papillary necrosis, nephrotic syndrome, tubulointerstitial nephritis, membranous glomerulonephritis, glomerulonephritis with minimal damage, glomerulonephritis.
• Fetal death, passage of amniotic fluid to the mother's bloodstream, potentially causing heart failure (anaphylactoid syndrome of pregnancy), incomplete abortion, premature birth, abnormal uterine contractions, retained placenta in the uterus after delivery.
• Abnormal uterine bleeding, uterine cramps, female infertility (decreased female fertility).
• Uterine rupture or perforation.

Reporting of side effects

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

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 after CAD. The expiration date is the last day of the month indicated.

Do not store at a temperature above25ºC.

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

Medicines should not be disposed of through drains or in the trash.Deposit the packaging and medicines that you no longer need at the SIGRE collection pointof the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need. In this way, you will help protect the environment.

Composition of Artrotec

• The active principles are: diclofenac sodium and misoprostol.
• The other components (excipients) are lactose monohydrate, microcrystalline cellulose, cornstarch without gluten, povidone, magnesium stearate, carboxymethylcellulose type C, sodium hydroxide, talc, triethyl citrate, crospovidone, anhydrous colloidal silica, and hydrogenated castor oil.

Appearance of the product and content of the container

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

Artrotec is presented in cold-molded aluminum blisters, containing 40 coated tablets per container.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

Pfizer, S.L.

Avda. de Europa, 20-B

Parque Empresarial La Moraleja,

28108 Alcobendas (Madrid).

Responsible for manufacturing:

Piramal Pharma Solutions (Dutch) B.V.

Level, 7e floor

Bargelaan 200

2333 CW

Leiden

Netherlands

Last review date of this leaflet: January 2025

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