Artrotec 50 mg/200 micrograms film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

ARTROTEC 50mg/200micrograms coated tablets

Diclofenac/Misoprostol

Read the entire 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 questions, ask your doctor or pharmacist.

• This medicine has been prescribed for you only, and must not be given to other people, even if they have the same symptoms as you, because it could be harmful to them.

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

Contents of the leaflet

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

1. What Artrotec is and what it is used for

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

Artrotec is used for the treatment of rheumatoid arthritis and osteoarthritis in patients at high risk of developing gastrointestinal lesions, such as elderly patients or those with a history of gastroduodenal ulcer.

2. What you need to know before taking Artrotec

Do not take Artrotec:

• if you are allergic to diclofenac or misoprostol, or to any of the other components of this medicine (listed in section 6).
• if you are allergic (hypersensitive) to acetylsalicylic acid (aspirin), other prostaglandins, or other non-steroidal anti-inflammatory drugs (NSAIDs).
• if you currently have an active stomach or duodenal ulcer, bleeding, or perforation.
• if you are pregnant, trying to become pregnant, or think you might 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 an obstruction or coronary bypass.
• if you are about to undergo heart surgery (bypass).
• if you have or have had circulatory problems (peripheral arterial disease).
• if you have severe renal or hepatic insufficiency.
• if you are a woman of childbearing age and are not using an effective contraceptive method to

prevent pregnancy (see section "Pregnancy" for further information).

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

• you think you may be allergic to sodium diclofenac, acetylsalicylic acid, ibuprofen, or any other NSAID, or to any of the other components of Artrotec (listed at the end of this leaflet). Signs of a hypersensitivity reaction include 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 that you use the lowest dose that relieves/controls your pain and that you do not take this medicine, Artrotec, for longer than necessary to control your symptoms.

Inform your doctor if you have recently undergone or are about to undergo stomach or intestinal surgery before receiving/taking/using Artrotec, as Artrotec may sometimes impair wound healing in the intestine after surgery.

Consult your doctor or pharmacist before starting to take Artrotec:

• If you have had or develop a stomach or duodenal ulcer, bleeding, or perforation, which may present as severe or persistent abdominal pain and/or black stools, or even without prior warning symptoms.

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

• If, during treatment with Artrotec, you develop a stomach or duodenal ulcer or bleeding, you must stop treatment and inform your doctor immediately.
• If you are elderly, have any type of cardiovascular disease, are being treated with acetylsalicylic acid, or have had or currently have gastrointestinal disorders, as you may be at increased risk of gastrointestinal complications.
• If you are pregnant or planning to become pregnant (see section "Pregnancy").

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

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

effective contraceptive methods while taking this medicine.

• Before taking diclofenac, ensure 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 concomitant medications that affect blood clotting or increase the risk of ulcers, such as oral anticoagulants or antiplatelet agents like acetylsalicylic acid (aspirin). You should also mention the use of other medicines that could increase the risk of such bleeding, such as corticosteroids, serotonin reuptake inhibitor antidepressants, and other non-steroidal anti-inflammatory drugs.
  • if you have Crohn's disease or ulcerative colitis, as medicines like Artrotec may worsen these conditions.
• Cardiovascular precautions

Medicines such as Artrotec may be associated with a moderate increase in the risk of heart attack ("myocardial infarction") or stroke, which can be serious and even fatal, especially when used at high doses and for prolonged periods. Do not exceed the recommended dose or duration of treatment.

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

In addition, these types of medicines may cause fluid retention, especially in patients with heart failure and/or high blood pressure (hypertension). Similarly, you should be cautious if you are prone to fluid retention.

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

• If, during treatment, and particularly in the first few months, you develop a skin rash, redness of the skin, or other allergy symptoms. In this case, you must stop treatment and inform your doctor immediately.
• If you have ever had a severe skin rash, skin peeling, blisters, or mouth sores after taking Artrotec or other painkillers.
• If you have liver (hepatic insufficiency), kidney (renal insufficiency), or heart (cardiac insufficiency) problems, inform your doctor before starting treatment, as closer monitoring may be necessary.
• If you are of childbearing age and are not using an effective contraceptive method. If you suspect you might be pregnant, treatment with Artrotec must be stopped and your doctor informed immediately.

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

Taking Artrotec with other medicines

Inform your doctor or pharmacist if you are currently using, or have recently used, any other medicines, including those obtained without a prescription, as well as herbal remedies.

If Artrotec is taken together with other medicines, its effect may be altered or its toxicity increased.

These include:

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

Taking Artrotec with food and drinks

The tablet should preferably be taken after main meals.

Pregnancy, breastfeeding and fertility

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

Pregnancy

Due to the potential risk of harm to the fetus, you must ensure you are not pregnant before starting treatment.

Artrotec is contraindicated in pregnant women as it induces uterine contractions associated with miscarriage, loss of amniotic fluid, premature birth, birth defects, and fetal death. Therefore, pregnancy must be ruled out before starting treatment with this medicine, and an effective contraceptive method must be used during treatment.

Your doctor will inform you of the risks if you become pregnant while taking Artrotec, 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 serious consequences for your child, particularly affecting 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 the pregnancy, close ultrasound monitoring of the pregnancy should be performed, with particular attention to the limbs and head.

For women of childbearing age, it should be noted that medicines like Artrotec have been associated with a reduced ability to conceive.

Breastfeeding

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

Artrotec must not be used if you are breastfeeding, as part of the medicine may pass into breast milk and cause undesirable 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 appropriate studies have not been conducted.

Artrotec contains lactose, hydrogenated castor oil, and sodium

This medicine contains lactose. If your doctor has informed 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 castor oil.

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; thus, it is essentially “sodium-free”.

3. How to take Artrotec

Follow exactly the instructions for use provided by your doctor.

If in doubt, consult your doctor or pharmacist again.

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

Adults

The recommended dose is one coated tablet two or three times daily, according to medical judgment.

Elderly patients

Dosage adjustment is not necessary for these patients.

Patients with impaired liver function or moderately impaired kidney function

Dosage adjustment is not necessary for these patients; however, treatment should be initiated with the lowest dose.

Use in children and adolescents

The efficacy and safety of this 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 contact the Toxicology Information Service at telephone number 91 562 04 20.

You may require medical attention. Inducing vomiting is advisable.

If you forget to take Artrotec

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

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

4. Possible adverse effects

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

Gastrointestinal effects

The most common adverse effects associated with medicines such as Artrotec are gastrointestinal: peptic ulcers, gastrointestinal perforation or bleeding (in some cases fatal), especially in elderly patients (see also section "Warnings and precautions"). Nausea, vomiting, diarrhoea, flatulence, constipation, heartburn, abdominal pain, blood in stools, vomiting blood, inflammation and ulcers in the mouth mucosa, and worsening of ulcerative colitis and Crohn's disease have also been observed (see also section "Warnings and precautions"). Gastritis has been observed less frequently.

Abdominal pain and diarrhoea occurred at the beginning of treatment, were generally transient and of mild to moderate intensity. Abdominal pain and diarrhoea may be reduced by taking Artrotec with food and avoiding the use of antacids containing magnesium.

Cardiovascular effects

Medicines such as Artrotec may be associated with an increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Oedema (fluid retention), high blood pressure, and heart failure have also been observed in association with treatment using medicines of the Artrotec type.

Skin effects

Medicines such as Artrotec may very rarely be associated with blistering reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

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

Hepatic effects

Medicines such as Artrotec may frequently be associated with increased 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 adverse effects reported with Artrotec was:

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

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

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

• Insomnia.
• Headache, dizziness.
• Gastrointestinal ulcer, duodenal inflammation, stomach inflammation, oesophagitis, gastrointestinal inflammation, vomiting, constipation, flatulence, belching.
• Skin rash, itching.
• Fetal malformations.
• Changes in certain blood parameters measuring liver function [elevated alanine aminotransferase (ALT), decreased haematocrit, increased alkaline phosphatase (ALP)].
• Low red blood cell count in blood tests (decreased haematocrit).

Uncommon adverse effects (may affect between 1 and 10 in 1,000 patients):

• Vaginal infection.
• Decreased number of platelets in the blood (thrombocytopenia).
• Stroke.
• Blurred vision.
• Myocardial infarction, heart failure.
• High blood pressure.
• Difficulty breathing (dyspnoea).
• Gastrointestinal bleeding, inflammation of the mouth mucosa (stomatitis).
• Red, raised, itchy skin lesions (urticaria), purplish spots on the skin and mucous membranes (purpura).
• Bleeding between menstrual periods (metrorrhagia), excessive or prolonged menstruation (menorrhagia), vaginal bleeding (which may occur after menopause), menstrual disorders.
• Fever, swelling (oedema), chills.
• Increased aspartate aminotransferase (AST), a blood enzyme measuring liver function.

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

• Severe allergic reaction (anaphylactic reaction).
• Nightmares.
• Inflammation of the pancreas (pancreatitis).
• Inflammation of the liver with or without yellowing of the skin (hepatitis with or without jaundice).
• Skin rash with blister formation (bullous dermatitis), swelling under the skin which may be severe (angioedema).
• Breast pain, painful menstruation (dysmenorrhoea).

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

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

Adverse effects with unknown frequency (cannot be estimated from available data):

• Haemolytic anaemia, decreased number of a type of blood cells called neutrophils (agranulocytosis), inhibition of platelet aggregation.
• Fluid retention.
• Mood changes.
• Aseptic meningitis (a condition characterised by headache, fever, and inflammation of the membranes covering the brain).
• Kounis syndrome.
• Inflammation of blood vessels (vasculitis).
• Gastrointestinal perforation.
• Severe impairment of liver function (liver failure), yellowing of the skin or whites of the eyes (jaundice), inflammation of the liver resulting in death (fulminant hepatitis).
• Skin and mucous membrane disease with blisters and lesions (erythema multiforme), skin inflammation with peeling (exfoliative dermatitis), skin and mucous membrane reactions, DRESS syndrome.
• Allergic skin reaction, which may include round or oval-shaped red and swollen skin patches, blisters, and itching (fixed drug eruption). Darkening of the skin in affected areas may also occur, which could persist after healing. Fixed drug eruption usually reappears in the same site(s) if the medicine is taken again.
• Severe impairment of kidney function (renal failure), kidney impairment, renal papillary necrosis, nephrotic syndrome, tubulointerstitial nephritis, membranous glomerulonephritis, minimal change glomerulonephritis, glomerulonephritis.
• Fetal death, amniotic fluid entering the maternal bloodstream possibly causing heart failure (anaphylactoid syndrome of pregnancy), incomplete abortion, premature newborn, abnormal uterine contractions, retention of the placenta in the uterus after childbirth.
• Abnormal uterine bleeding, uterine cramps, female infertility (reduced female fertility).
• Rupture or perforation of the uterus.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is an effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Artrotec

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

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date is the last day of the month indicated.

Do not store above 25°C.

Keep in the original packaging. Do not use Artrotec if you notice that the packaging is damaged or opened.

Medicines must not be disposed of via wastewater or household waste. Return any unused medicines and their containers to the SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of unused medicines and their packaging. This will help protect the environment.

6. Package contents and other information

Composition of Artrotec

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

Appearance of the product and contents of the pack

Artrotec is presented as biconvex, round, coated tablets, white in colour, with a diameter of approximately 10–11 mm, marked with “ ” on one side and “Searle 1411” on the other.

Artrotec is supplied in cold-formed aluminium blisters containing 40 coated tablets per pack.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Pfizer, S.L.

Avda. de Europa, 20-B

Parque Empresarial La Moraleja,

28108 Alcobendas (Madrid), Spain

Manufacturer:

Piramal Pharma Solutions (Dutch) B.V.

Level, 7e verdieping

Bargelaan 200

2333 CW

Leiden

The Netherlands

Date of the most recent review of this leaflet: September 2025

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