ArtroTec

Package leaflet: Information for the patient

Artrotec 75 modified-release tablets

diclofenac sodium, misoprostol
Please read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. 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. Do not give it to others, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this 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 side 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 used for the symptomatic treatment of rheumatoid arthritis and osteoarthritis, and may be beneficial in protecting patients at risk of irritation or ulceration of the stomach or intestine.
Artrotec contains diclofenac and misoprostol. Diclofenac belongs to a class of medicines called non-steroidal anti-inflammatory drugs (NSAIDs).
Although NSAIDs relieve pain, they also reduce the production of natural protective substances called prostaglandins found in the stomach lining.
This means that NSAIDs can cause stomach problems or stomach ulcers. Artrotec also contains misoprostol, which is very similar to prostaglandins and can help protect the stomach.

2. What you need to know before taking Artrotec

Do not take Artrotec if:

• you think you are allergic to diclofenac sodium, aspirin (acetylsalicylic acid), ibuprofen, or any other NSAID, to misoprostol or another prostaglandin-containing medicine, or to any of the excipients of Artrotec (see section 6). Signs of a hypersensitivity reaction include skin rash, swelling or itching of the skin, swelling of the face and mouth (angioedema), severe nasal congestion, asthma (breathing problems), chest pain, wheezing, or any other allergic-type reaction
• you currently have a stomach or intestinal ulcer or perforation
• you currently have bleeding in the stomach, intestine, or brain
• you are about to undergo or have recently undergone coronary artery bypass graft (CABG) surgery
• you have severe liver or kidney failure
• 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 if you have undergone a procedure to remove or bypass these blockages
• you have had or have circulation problems (peripheral arterial disease)
• you are pregnant, or planning to become pregnant, because the medicine may cause miscarriage. Women of childbearing potential must use adequate contraceptive measures while taking Artrotec
• you are a woman of childbearing potential and are not using an effective method of contraception to prevent pregnancy (see section "Pregnancy" for further information).

Warnings and precautions
Talk to your doctor or pharmacist before taking Artrotec if:

• you have other health problems such as liver or kidney disease. Do not take Artrotec if you have severe renal or hepatic failure
• you have previously had a stomach or intestinal ulcer or bleeding. Do not take Artrotec if you currently have a stomach or intestinal ulcer or bleeding
• you are prone to episodes of bleeding or bruising easily
• you have inflammation of the intestine (ulcerative colitis or Crohn's disease)
• you have or have ever had asthma or an allergic condition
• you have an infection, as Artrotec may mask fever or other signs of infection
• you are dehydrated
• you are over 65 years old, as your doctor will need to monitor you regularly
• you are pregnant or planning to have a child (see section "Pregnancy"). Treatment with Artrotec must be stopped immediately due to the risk to the fetus.
• you are a woman of childbearing potential (see also section on "Pregnancy"). It is important to use effective contraceptive measures while taking this medicine
• 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 following surgery.

NSAIDs such as Artrotec can cause bleeding or ulcers. If this occurs, treatment must be discontinued.
The use of Artrotec in combination with another NSAID other than aspirin (e.g. ibuprofen) may further increase the frequency of ulcers or gastrointestinal bleeding.
If you are taking a corticosteroid (e.g. prednisone), an oral anticoagulant, or a selective serotonin reuptake inhibitor (e.g. sertraline), or if you consume alcohol, Artrotec may cause serious adverse effects, particularly complications affecting the stomach and intestine.
Make sure your doctor knows before prescribing Artrotec:

• if you smoke
• if you have diabetes
• if you have angina, blood clots, high blood pressure, high cholesterol, or high triglycerides.

Medicines such as Artrotec may be associated with a slight increase in the risk of heart attack (myocardial infarction) or stroke. The risk increases with higher doses and prolonged treatment. Do not exceed the recommended dose or duration of treatment.
Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary.
As with other NSAIDs (e.g. ibuprofen), Artrotec may lead to increased blood pressure, and therefore your doctor may ask you to monitor your blood pressure regularly.
If you have heart, liver, or kidney problems, your doctor will monitor you periodically.

Other medicines and Artrotec
Some medicines may affect how others work. Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including:

• Aspirin (acetylsalicylic acid) or other NSAIDs (e.g. ibuprofen)
• Medicines used to treat osteoarthritis or rheumatoid arthritis, known as cyclooxygenase-2 (COX-2) inhibitors
• Diuretics (used to treat excess fluid in the body)
• Cyclosporine or tacrolimus (used to suppress the immune system, e.g. after transplantation)
• Lithium (used to treat certain types of depression)
• Digoxin (a medicine used for irregular heartbeat and/or heart failure)
• Warfarin or other oral anticoagulants (medicines that reduce blood clotting, e.g. aspirin)
• Medicines used to treat anxiety and depression called Selective Serotonin Reuptake Inhibitors (SSRIs)
• Medicines used to control blood sugar levels (oral hypoglycemics for diabetes)
• Methotrexate (used to treat rheumatoid arthritis, psoriasis, and leukemia)
• Steroid-containing medicines (e.g. corticosteroids, often used as anti-inflammatory agents)
• Medicines for high blood pressure (antihypertensives)
• Antacids containing magnesium (used to treat heartburn and indigestion)
• Quinolone antibiotics (used to treat certain infections)
• Ketoconazole, fluconazole, miconazole, and voriconazole (used to treat certain fungal infections)
• Amiodarone (used to treat heart rhythm abnormalities)
• Sulfinpyrazone (used to treat gout)
• If you have taken a medicine called mifepristone (used to terminate pregnancy) within the last 12 days. Artrotec must not be taken until 8–12 days after taking mifepristone.

Pregnancy, breastfeeding, and fertility

Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, do not take Artrotec. If you are planning a pregnancy, inform your doctor. Because of the potential risk of harm to the fetus, you must ensure you are not pregnant before starting treatment. Women of childbearing potential must use adequate contraceptive measures while taking Artrotec.
Your doctor will inform you of the risks if you become pregnant while taking Artrotec, as it may cause miscarriage, premature birth, or fetal malformations (congenital defects). You must NEVER take this medicine if you are pregnant, as it may have serious consequences for the baby, 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, careful ultrasound monitoring of the pregnancy must be performed, with particular attention to limbs and head.

Breastfeeding
If you are breastfeeding, consult your doctor or pharmacist before taking this medicine. Do not use Artrotec during breastfeeding.

Driving and use of machinery
If you feel dizzy or drowsy after taking Artrotec, do not drive or operate tools or machinery until these effects have disappeared.

Artrotec contains
Lactose (a type of sugar). If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking Artrotec.

3. How to take Artrotec

Always take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts,
consult your doctor or pharmacist.
Take one tablet twice a day.
Artrotec tablets must be swallowed whole with a glass of water (do not chew), during or
after meals.
Elderly patients and patients with kidney or liver problems: your doctor may monitor you more closely.
No dose adjustment is necessary.
Use in children: Artrotec is intended only for adults. It must not be used in children (under 18
years of age).
If you take more Artrotec than you should
Do not take more tablets than prescribed by your doctor. If you take too many tablets, contact your doctor,
pharmacist, or go to hospital as soon as possible, and bring the medicine with you.
If you forget to take Artrotec
If you forget to take a tablet, take it as soon as you remember. Do not take a double dose to
compensate for the missed dose.
If you stop taking Artrotec
Do not stop taking Artrotec unless your doctor tells you to. If you have any doubts about using this
medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
If you are concerned about side effects, speak to your doctor. It is important that you know what might
occur so that you can take action if Artrotec causes a side effect. Artrotec sometimes causes side effects,
but these usually disappear during treatment as your body gets used to the medicine.

If any of the following conditions occur, stop taking Artrotec and contact your doctor immediately:
If you have

• Weakness or inability to move one side of the body, slurred speech (stroke), chest pain (heart attack), heart failure, or palpitations (awareness of your heartbeat) – the frequency of these events is uncommon
• Shortness of breath – the frequency of these events is uncommon
• Artrotec may cause a reduction in a type of white blood cells (which help protect the body from infections and diseases), potentially leading to infections with symptoms such as chills, sudden fever, sore throat, or flu-like symptoms – the frequency of these events is uncommon
• Severe stomach pain or any sign of bleeding or injury to the stomach or intestine, such as black stools or blood in the stool – the frequency of these events is uncommon, or vomiting blood – this occurs rarely
• A serious skin reaction such as rash, blistering, or peeling of the skin (DRESS syndrome, Stevens-Johnson syndrome, exfoliative dermatitis, or toxic epidermal necrolysis) – the frequency of these events is not known
• A severe allergic reaction such as rash, facial swelling, wheezing, or difficulty breathing (anaphylactic shock) – this occurs rarely
• Jaundice (yellowing of the skin or whites of the eyes) – this occurs rarely
• Reduction in the number of platelets in the blood (increasing the risk of bleeding or bruising) – the frequency of these events is not known
• Symptoms of meningitis (stiff neck, headache, nausea (feeling unwell), vomiting, fever, or loss of consciousness) – the frequency of these events is not known
• Chest pain, which may indicate a potentially serious allergic reaction called Kounis syndrome – the frequency of this event is not known

If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist.

• Very common: may affect more than 1 in 10 people
• Stomach discomfort, diarrhoea, nausea, indigestion

Diarrhoea is the most common problem and can sometimes be severe. Taking Artrotec with food reduces the likelihood of diarrhoea. If you use an antacid (a substance to reduce stomach acidity), avoid antacids containing magnesium, as they may worsen diarrhoea. Your pharmacist can help you choose a suitable antacid. If diarrhoea persists and is severe, inform your doctor.

• Common: may affect up to 1 in 10 people

• Rash, itching

• Vomiting, flatulence, constipation, belching, gastritis (indigestion, stomach discomfort, vomiting)

• Stomach or intestinal ulcers

• Headache, dizziness

• Difficulty sleeping

• Changes in liver blood tests

• Inflammation of the digestive tract, including the intestine, such as nausea, diarrhoea, abdominal pain

• Abnormal fetal development

• Uncommon: may affect up to 1 in 100 people

• Swelling of the mouth

• Fluid retention in the body, which may cause swollen legs and ankles

• Abnormal or unexpected vaginal bleeding, menstrual disorders

• Reduction in the number of platelets in the blood (increased risk of bleeding or bruising)

• Purpura (purple spots on the skin)

• Urticaria (itchy skin rash)

• Vaginal infection (itching, burning, redness, pain, especially during sexual intercourse or while urinating)

• Blurred vision

• High blood pressure

• Loss of appetite

• Menstrual disorders, such as unusually heavy or light bleeding, or delayed menstrual cycle

• Chills or fever

• Tremor, drowsiness, fatigue

• Ringing in the ears

• Depression and feelings of anxiety

• Tingling or prickling sensations (pins and needles)

• Mouth ulcers and dry mouth

• Rare: may affect up to 1 in 1,000 people

• Inflammation of the liver (possible yellowing of the skin, headache, fever, chills, generalized weakness)

• Inflammation of the pancreas, causing severe abdominal and back pain

• Lung inflammation such as cough, increased sputum production

• Breast pain

• Vomiting blood

• Worsening of ulcerative colitis (inflammation of the lower intestine)

• Damage to the oesophagus

• Swollen tongue

• Low blood pressure

• Hair loss

• Increased sensitivity to light

• Nightmares

• Very rare: may affect up to 1 in 10,000 people

• Severe liver disorders, including liver failure

• Not known: frequency cannot be estimated from the available data

• Worsening of Crohn’s disease (inflammation of the intestine)

• Kidney problems

• Seizures

• Inflammation of blood vessels (which may cause fever, pain, purple spots)

• Psychotic disorder (mental disorder characterized by loss of contact with reality)

• Mood changes, irritability, memory problems, feeling confused

• Vision difficulties, taste disturbances

• Inflammation

• Abnormal uterine contractions, uterine rupture, retained placenta after childbirth, life-threatening maternal reaction due to amniotic fluid (the fluid surrounding the fetus) or other fetal material entering the maternal bloodstream, uterine bleeding, miscarriage, neonatal death, premature birth

• Anaemia (low number of red blood cells), which may cause pale skin and lead to weakness or shortness of breath

• Menstrual pain/uterine cramps

• Reduced fertility in women

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. You can also report side effects directly via the national reporting system at: http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Artrotec

Keep this medicine out of the sight and reach of children.
Do not store above 25 °C. Store in the original packaging.
Do not use this medicine after the expiry date which is stated on the blister and on the packaging. The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Artrotec contains
The active substances are diclofenac sodium and misoprostol.
Each tablet contains 75 mg of diclofenac sodium and 0.2 mg of misoprostol.
The excipients are:
Monohydrate lactose, microcrystalline cellulose, maize starch, povidone K-30, magnesium stearate,
methacrylic acid copolymer type C, sodium hydroxide, talc, triethyl citrate, hypromellose, crospovidone,
anhydrous colloidal silica and hydrogenated castor oil.
Description of the appearance of Artrotec and package contents
Artrotec is available as white, round, biconvex tablets, marked on one side
“SEARLE” and “1421”, and on the other side “75” surrounded by four “A”s.
The tablets are packaged in blisters contained in cartons of 10, 20, 30, 60, 90, 100 and 140
tablets.
It is possible that not all pack sizes are marketed.
Marketing Authorization Holder
Pfizer Italia S.r.l.
Via Isonzo, 71 – 04100 Latina
Manufacturer:
Piramal Healthcare UK Limited
Morpeth
Northumberland
NE61 3YA
United Kingdom
Piramal Pharma Solutions (Dutch) B.V.
Level, 7e verdieping
Bargelaan 200
2333 CW
Leiden
The Netherlands

Patient Information Leaflet

Artrotec 50 mg + 200 mcg tablets

Diclofenac/misoprostol
Please read this entire leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be dangerous.
• If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this 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 side 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 contains the active substances diclofenac and misoprostol. Diclofenac belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs) and works by reducing inflammation and pain. Misoprostol is a substance similar to prostaglandins (naturally produced within the body) that protects the lining of the stomach and intestine from potential problems caused by diclofenac.

Artrotec is used in the treatment of:

• rheumatoid arthritis and osteoarthritis (chronic inflammatory rheumatic diseases of the joints);
• ankylosing spondylitis (rheumatic condition affecting the spine);
• inflammations of non-rheumatic origin or resulting from trauma.

Artrotec is indicated for patients who have stomach or intestinal problems (e.g. gastritis with erosions of the inner stomach wall, previous episodes of injury (ulcer) to the stomach or intestine, bleeding from the oesophagus, stomach and/or the first part of the intestine (small intestine), previous stomach problems due to the use of this type of medicine (NSAIDs)), in whom it is considered essential to use non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac.

2. What you should know before taking Artrotec

Do not take Artrotec

• if you think you are allergic to sodium diclofenac, aspirin (acetylsalicylic acid), ibuprofen, or any other NSAID, to misoprostol or any other prostaglandin-based medicine, or to any of the excipients of Artrotec (see section 6). Signs of a hypersensitivity reaction include skin rash, swelling or itching of the skin, swelling of the face and mouth (angioedema), severe nasal congestion, asthma (breathing problems), chest pain, wheezing, or any other allergic-type reaction;
• if you have previously had episodes of bleeding or perforation in the stomach or intestine caused by prior treatment with NSAIDs, or if you have previously suffered from recurrent episodes of bleeding or damage to the stomach or intestinal wall (peptic ulcer), i.e., if you have had two or more distinct episodes of ulceration or bleeding confirmed by a doctor;
• if you have heart disease, i.e., if your heart is unable to pump an adequate amount of blood to the body (established congestive heart failure), or if you have blood vessel blockages leading to the heart or have had a heart attack (ischemic heart disease) and/or suffer from circulation problems in the brain or have had a stroke (cerebrovascular disease);
• if you suffer from circulation problems in the body (peripheral arterial disease);
• if you are or think you may be pregnant;
• 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); if you are breastfeeding.

Warnings and precautions
Talk to your doctor or pharmacist before taking Artrotec if any of the following apply to you:

• you suffer from chronic inflammation of the intestine (ulcerative colitis or Crohn’s disease);
• you have heart problems or believe you are at risk of such conditions (e.g., you have high blood pressure, elevated cholesterol and/or triglycerides, diabetes, blood clots in blood vessels (thrombi) that may lead to myocardial infarction or stroke, suffer from chest pain (angina), or smoke). If you have high blood pressure, your doctor will closely monitor your blood pressure throughout treatment; you are prone to episodes of bleeding or bruising;
• you have liver or kidney problems. If liver or kidney problems worsen, discontinue treatment with this medicine;
• you are pregnant or planning to become pregnant (see section “Pregnancy”). Treatment with Artrotec must be stopped immediately due to the risk to the fetus;
• you are a woman of childbearing age (see also section on “Pregnancy”). It is important to use effective contraceptive measures while taking this medicine;
• if you have recently undergone or are about to undergo surgery on the stomach or intestinal tract before receiving/using Artrotec, as Artrotec may sometimes impair wound healing in the intestine following surgery.

Artrotec may cause:

• bleeding, injuries (ulcers), or perforations in the stomach and/or intestine, even without warning symptoms or previous serious stomach or intestinal problems, which may be life-threatening. In such a case, consult your doctor and discontinue treatment. If you have previously suffered from these problems or have cardiovascular issues, if you are taking aspirin, corticosteroids, medicines that inhibit blood clotting (anticoagulants), or medicines for anxiety and depression (called selective serotonin reuptake inhibitors) (see “Other medicines and Artrotec”), if you are over 65 years old, or if you consume alcohol, your risk of experiencing these adverse effects is higher. If you are over 65 years old (elderly) or have previously had gastrointestinal ulcers (see “Do not take Artrotec”), your doctor will advise starting treatment with the lowest available dose;
• a modest increase in the risk of heart attack (myocardial infarction) or stroke. These events are serious and may sometimes lead to death. The risk increases with higher doses and prolonged treatment. Never exceed the recommended dose or duration of treatment;
• increased blood pressure, so your doctor may ask you to monitor your blood pressure regularly;
• fluid retention in the body and swelling, especially in the legs and feet;
• serious skin reactions, sometimes fatal, characterized by blisters, lesions, and peeling of the skin (such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis). Discontinue treatment immediately if you develop a skin rash, lesions, or any other skin problems.

If you have heart, liver, or kidney problems, or if you are over 65 years old, your doctor will perform periodic checks of kidney function and prescribe the lowest possible dose (see section 3 “How to take Artrotec”).
If you are undergoing long-term treatment, your doctor will perform periodic checks (e.g., kidney and liver function tests, blood tests).
The adverse effects caused by Artrotec can be minimized by using the lowest effective dose for the shortest necessary duration.

Children
The safety and efficacy of this medicine have not been established in children.

Elderly
If you are over 65 years old, you have a higher likelihood of experiencing adverse effects during treatment with Artrotec, particularly bleeding and perforations of the stomach and/or intestine, which may be fatal (see section 3 “How to take Artrotec”). Your doctor will prescribe the lowest possible dose and monitor you regularly during treatment.

Other medicines and Artrotec
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
The following medicines may affect the efficacy and/or toxicity of Artrotec, or Artrotec may affect the efficacy and/or toxicity of the following medicines:

• corticosteroids, medicines used to treat inflammation;
• acetylsalicylic acid (aspirin);
• other non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors;
• oral anticoagulants (e.g., warfarin, apixaban, dabigatran, and rivaroxaban), medicines that reduce blood clotting;
• antiplatelet agents, medicines used to reduce/inhibit platelet aggregation;
• selective serotonin reuptake inhibitors (SSRIs), medicines used to treat anxiety and depression;
• diuretics, medicines used to increase urine production;
• ACE inhibitors, angiotensin II antagonists, and beta-blockers, medicines used to lower blood pressure. Your doctor will carefully evaluate whether to prescribe these medicines together with Artrotec, especially if you are elderly or have kidney problems;
• cyclosporine or tacrolimus, medicines used to suppress the immune system, e.g., after organ transplantation. If you need to take these medicines together with Artrotec, your doctor will closely monitor your kidney function. In the case of concomitant use of Artrotec and cyclosporine, your doctor may decide to prescribe the lowest recommended dose of Artrotec;
• digoxin, a medicine used for irregular heartbeat and/or heart failure;
• oral hypoglycemics, medicines used to lower blood sugar levels;
• lithium, a medicine used to treat certain types of depression;
• methotrexate, a medicine used to treat rheumatoid arthritis, psoriasis, and leukemia;
• voriconazole, sulfinpyrazone, or other medicines that reduce the metabolism of diclofenac (the active ingredient in Artrotec) in the body, as they may lead to increased effects of the medicine. Your doctor will prescribe the lowest recommended dose of Artrotec.

Pregnancy, breastfeeding, and fertility

Pregnancy
Do not take Artrotec if you are pregnant, suspect you may be pregnant, or are planning a pregnancy.
Do not take Artrotec if you are or think you may be pregnant (see section 2 “Do not take Artrotec”), as it may endanger the pregnancy (increased risk of miscarriage), fetal development (increased risk of birth defects), and your health (delayed or prolonged labor and increased risk of prolonged bleeding during delivery). Due to the potential risk of harming the fetus, you must ensure you are not pregnant before starting treatment.
If you are a woman of childbearing age, you must use effective contraceptive methods to avoid pregnancy during treatment with this medicine.
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 defects). You must NEVER take this medicine if you are pregnant, as it may have serious consequences for the baby, 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, careful ultrasound monitoring of the pregnancy is required, with particular attention to limbs and head.

Breastfeeding
Do not take Artrotec if you are breastfeeding, as the active ingredients in Artrotec pass into breast milk.
If you are breastfeeding, consult your doctor or pharmacist before taking this medicine.

If you take Artrotec or similar medicines (called non-steroidal anti-inflammatory drugs or NSAIDs) during the second or third trimester of pregnancy, renal abnormalities in the fetus may occur, resulting in reduced amniotic fluid volume (oligo-hydramnios), which may be severe.
If you use this medicine, you will need to be closely monitored to assess amniotic fluid volume.

Artrotec may cause reversible infertility. Do not take this medicine if you intend to become pregnant, if you have fertility problems, or if you are undergoing fertility investigations.

Driving and using machines
It is not known whether Artrotec affects the ability to drive or use machinery.

Artrotec contains lactose
Artrotec contains lactose, a type of sugar. If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking this medicine.

3. How to take Artrotec

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Adults: The recommended dose is 1 tablet 2–3 times daily.
Artrotec tablets must be swallowed whole with a glass of water (do not chew) during meals.
If you are over 65 years of age (elderly) or have kidney or liver problems: you do not need to take a different dose than that recommended for an adult. However, your doctor may decide to start treatment with the lowest possible dose for you.
If you have severe kidney or liver problems, your doctor will monitor you closely (see section Undesirable effects).
Use in children
The safety and efficacy of ARTROTEC in children have not been established.
Undesirable effects can be minimized by taking the lowest possible dose for the shortest possible time needed to control your symptoms (see "Precautions for use").
If you take more Artrotec than you should
If you accidentally ingest/overdose on Artrotec, contact your doctor immediately or go to the nearest hospital.
Symptoms may include drowsiness, tremor, convulsions, difficulty breathing, abdominal pain, diarrhoea, fever, palpitations, low blood pressure, and slowed heart rate.
If you forget to take Artrotec
Do not take a double dose to make up for the forgotten dose.
If you stop taking Artrotec
Do not stop treatment with Artrotec unless instructed by your doctor.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Stop taking Artrotec and contact your doctor immediately if you experience:

• severe stomach pain or any sign of bleeding, ulceration, or perforation of the stomach or intestine, such as black stools, blood in stools or vomit. Gastrointestinal perforation and bleeding can sometimes be fatal, especially in the elderly (see "Warnings and precautions");
• serious skin reaction such as rash, blisters, necrosis or peeling of the skin, mucosal lesions (DRESS syndrome, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis, mucocutaneous reactions) – the frequency of these events is unknown;
• worsening of ulcerative colitis or Crohn's disease (inflammation of the intestine);
• severe allergic reaction such as rash, facial swelling, wheezing or difficulty breathing (anaphylactic shock and angioedema);
• heart attack;
• kidney problems (renal failure or impairment, renal papillary necrosis, nephrotic syndrome, tubulointerstitial nephritis, membranous glomerulonephritis, minimal lesion glomerulopathy);
• stroke;
• jaundice (yellowing or yellowish discoloration of the skin and whites of the eyes);
• chest pain, which may be a sign of a potentially serious allergic reaction called Kounis syndrome – the frequency of this event is unknown.

Contact your doctor if you experience any of the following side effects:
Very common (may affect more than 1 in 10 people):

• abdominal pain, diarrhoea, nausea, and indigestion. You can reduce the likelihood of diarrhoea by taking Artrotec with food and by avoiding antacids (substances used to reduce stomach acidity) containing magnesium taken at the same time.

Common (may affect up to 1 in 10 people):

• difficulty sleeping
• headache, dizziness
• inflammation of the duodenum (a part of the intestine), gastritis, oesophagitis
• inflammation of the stomach and intestine
• vomiting, constipation, flatulence, belching
• rash, itching
• abnormal blood test results related to liver function
• reduced haematocrit (a blood test measuring the proportion of blood volume made up of red blood cells)
• Abnormal fetal development

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

• inflammation of the vagina
• reduced number of platelets in the blood (thrombocytopenia)
• blurred vision
• heart failure
• high blood pressure
• difficulty breathing (dyspnoea)
• mouth ulcers (stomatitis)
• urticaria, purpura (reddish-brown spots on the skin)
• very heavy menstrual periods (menorrhagia) or heavy bleeding between periods (metrorrhagia), vaginal bleeding (which may also occur after menopause), menstrual disorders
• fever
• swelling (oedema)
• chills
• increased aspartate aminotransferase, a blood test value related to liver function

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

• nightmares
• inflammation of the pancreas (pancreatitis)
• inflammation of the liver (hepatitis)
• blistering skin eruptions (bullous eruption)
• breast pain
• increased severity of menstrual pain

Frequency not known (frequency cannot be estimated from the available data):

• anaemia
• reduced number of white blood cells
• inhibition of platelet aggregation leading to increased risk and duration of bleeding
• fluid retention in the body, which may cause swelling of the ankles and legs
• mood changes
• inflammation of the membranes covering the brain (aseptic meningitis)
• inflammation of blood vessels
• liver failure
• fetal death, a life-threatening reaction in the mother due to the passage of amniotic fluid (the fluid surrounding the fetus) or other fetal material into the maternal bloodstream (anaphylactoid syndrome of pregnancy), abortion, premature birth, abnormal uterine contractions, placental or membrane retention
• uterine haemorrhage, uterine cramps
• infertility or reduced fertility in women
• rupture/perforation of the uterus

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at: http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Artrotec

Keep this medicine out of the sight and reach of children.
Do not store above 25 °C.
Keep in the original packaging to protect the medicine from moisture.
Do not use this medicine after the expiry date stated on the carton and blister after "Exp.".
The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Artrotec contains
The active substances are diclofenac and misoprostol.
Each tablet contains 50 mg of diclofenac and 200 mcg of misoprostol.
The other components are: lactose, microcrystalline cellulose, corn starch, polyvinylpyrrolidone K-30,
magnesium stearate, methacrylic acid copolymer C, sodium hydroxide, talc, triethyl citrate, methylhydroxypropyl
cellulose, insoluble polyvinylpyrrolidone, anhydrous colloidal silica and hydrogenated castor oil.
Description of the appearance of Artrotec and the contents of the pack
Artrotec tablets are packaged in Al/PVC blisters contained in cartons of 10, 30 and 60 tablets.
Not all pack sizes may be marketed.
Marketing Authorization Holder
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina
Manufacturer
Piramal Healthcare UK Limited.
Whalton Road, Morpeth
Northumberland
United Kingdom
Piramal Pharma Solutions (Dutch) B.V.
Level, 7e verdieping
Bargelaan 200
2333 CW
Leiden
Netherlands