Arthrotec

Package Leaflet: Information for the Patient

Warning! Keep the leaflet! Information on the immediate packaging in a foreign language.

ARTHROTEC, 50 mg + 0.2 mg, tablets

Diclofenac sodium + Misoprostol

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if necessary.
• In case of any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

• 1. What is ARTHROTEC and what is it used for
• 2. Important information before taking ARTHROTEC
• 3. How to take ARTHROTEC
• 4. Possible side effects
• 5. How to store ARTHROTEC
• 6. Contents of the pack and other information

1. What is ARTHROTEC and what is it used for

ARTHROTEC is a nonsteroidal anti-inflammatory drug (NSAID).
ARTHROTEC is indicated for use in patients who require concomitant use of a nonsteroidal anti-inflammatory drug (diclofenac) and misoprostol.
Diclofenac in ARTHROTEC is indicated for the symptomatic treatment of osteoarthritis and rheumatoid arthritis. Misoprostol is indicated for the treatment of patients who require prophylaxis against gastric and/or duodenal ulcers caused by the use of NSAIDs.

2. Important information before taking ARTHROTEC

When not to take ARTHROTEC:

• if the patient is allergic to diclofenac, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs (NSAIDs), misoprostol, other prostaglandins, or any of the other ingredients of this medicine (listed in section 6); Hypersensitivity symptoms include, among others, chest pain;
• in case of active gastric and/or duodenal ulcer disease, perforation, or bleeding;
• in case of other active bleeding, such as cerebral vascular bleeding;
• in pregnancy or in women planning to become pregnant;
• if the patient is of childbearing age and does not use effective contraception to prevent pregnancy (for additional information, see the section on "Pregnancy");
• in patients in whom NSAIDs cause asthma attacks, urticaria, or acute rhinitis;
• for the treatment of postoperative pain in coronary artery bypass grafting;
• if the patient has been diagnosed with heart disease and/or cerebrovascular disease, such as moderate or severe heart failure, myocardial infarction, stroke, transient cerebral ischemia, or vascular thrombosis of the heart or brain, or after revascularization or coronary artery bypass grafting;
• if the patient has or has had circulatory disorders (peripheral vascular disease);
• in patients with severe renal or hepatic impairment.

Warnings and precautions

Before starting treatment with ARTHROTEC, the patient should discuss it with their doctor or pharmacist.
If the patient:

• is pregnant or plans to become pregnant (see the section on "Pregnancy"); due to the risk to the fetus, taking ARTHROTEC should be stopped immediately;
• is of childbearing age (see the section on "Pregnancy"); due to the risk to the fetus, it is essential to use effective contraception during treatment with ARTHROTEC.

Special caution when taking ARTHROTEC

• in patients with renal, hepatic, or severe heart disorders, as well as in the elderly. In cases of severe hepatic impairment, significant dehydration, ARTHROTEC should only be used in exceptional cases and under close monitoring of the patient's condition (see the section "When not to take ARTHROTEC");
• when taking high doses of diclofenac (150 mg per day) and long-term treatment, as this may be associated with an increased risk of serious arterial thrombotic events (e.g., myocardial infarction or stroke). The doctor should inform the patient about the symptoms and/or signs of serious cardiovascular toxicity and the actions to be taken in case of such symptoms;
• in patients who have had symptoms of toxic effects on the gastrointestinal tract or gastric and/or duodenal ulcer disease in the past. In particular, elderly patients should report any unusual abdominal symptoms (especially gastrointestinal bleeding) early in the treatment phase. If gastrointestinal bleeding or ulcers occur, the doctor will decide whether to discontinue the combined drug containing diclofenac and misoprostol;
• in patients with blood disorders or impaired coagulation, as well as in patients with a history of cerebral vascular bleeding, as ARTHROTEC, like other NSAIDs, may reduce platelet aggregation and prolong bleeding time;
• in patients taking anticoagulant medications: warfarin and/or coumarin derivatives and new oral anticoagulants (e.g., apixaban, dabigatran, rivaroxaban) due to the increased risk of gastrointestinal bleeding and other bleeding;
• in patients with ulcerative colitis or Crohn's disease, as ARTHROTEC may exacerbate symptoms of these diseases;
• in patients with asthma or allergic disease - currently or in the past, as NSAIDs may cause bronchospasm in patients with asthma or allergic disease;
• in patients with hypertension and/or mild heart failure, as NSAIDs have been observed to cause fluid retention and edema in this patient population. The doctor will provide the patient with information on monitoring and other special recommendations.

Concomitant use of ARTHROTEC and other systemically administered NSAIDs, except for acetylsalicylic acid, including selective COX-2 inhibitors (e.g., rofecoxib, celecoxib), should be avoided due to the increased frequency of gastrointestinal ulcers and bleeding.
Before taking ARTHROTEC, the patient should tell their doctor if they have recently undergone or are scheduled to undergo stomach or gastrointestinal surgery, as ARTHROTEC may sometimes cause impaired wound healing in the intestines after surgery.
ARTHROTEC may cause serious gastrointestinal side effects, including inflammation, bleeding, ulcers, and perforation of the stomach, small intestine, and large intestine, which can be fatal. If gastrointestinal bleeding or ulcers occur, treatment with ARTHROTEC should be discontinued. These events may occur at any time during treatment, with or without warning symptoms, or in patients with a history of serious gastrointestinal side effects.
The group at highest risk of developing these gastrointestinal complications associated with ARTHROTEC includes patients receiving high doses of the medicine, elderly patients, patients with cardiovascular disorders, patients taking concomitant acetylsalicylic acid, corticosteroids, selective serotonin reuptake inhibitors, patients consuming alcohol, or patients with gastrointestinal diseases, active or in the past, such as ulcers, gastrointestinal bleeding, or inflammation of the gastrointestinal mucosa.
Therefore, ARTHROTEC should be used with caution in these patients, starting treatment with the lowest effective dose.
ARTHROTEC should not be used in premenopausal women unless they use effective methods of contraception and have been informed of the risks associated with taking the medicine during pregnancy. There is a warning on the packaging: "Do not use in women of childbearing age, unless they use effective contraception".
Taking such medications as ARTHROTEC may be associated with a slight increase in the risk of heart attack (myocardial infarction) or stroke. This risk increases with long-term use of high doses of the medicine. Do not use higher doses or longer treatment than recommended.
Rarely, serious skin reactions have been observed during treatment with NSAIDs, including ARTHROTEC. The patient should immediately report any skin changes to their doctor. The doctor may decide to discontinue treatment with ARTHROTEC in case of the first occurrence of a skin rash, mucosal lesions, or any other symptoms of hypersensitivity.
In patients with systemic lupus erythematosus and connective tissue diseases, ARTHROTEC may increase the risk of developing aseptic meningitis.
During long-term treatment with high doses of pain and/or anti-inflammatory medication, headache may occur, which should not be treated by administering further doses of the medicine or other NSAIDs.
ARTHROTEC may mask fever, and thus the underlying disease.
The medicine may make it difficult to become pregnant. If the patient plans to become pregnant or has problems becoming pregnant, they should inform their doctor.
ARTHROTEC may cause vision disturbances. In case of vision disturbances, the patient should contact an ophthalmologist.
Before taking the medicine, the patient should inform their doctor:

• if they smoke,
• if they have diabetes,
• if they have angina, thrombosis, hypertension, high cholesterol, or high triglycerides.

The occurrence of side effects can be reduced by using the medicine in the lowest effective dose and for no longer than necessary.

ARTHROTEC and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
The patient should inform their doctor if they are taking:

• diuretics (diuretic medications): NSAIDs may reduce the effectiveness of diuretics. When taking potassium-sparing diuretics, hyperkalemia may occur;
• cyclosporine (immunosuppressive medications used, among others, in the treatment of transplant patients): diclofenac may increase the nephrotoxicity of cyclosporine; it is essential to start treatment with ARTHROTEC at the lowest dose and closely monitor the patient's condition for signs of toxic effects;
• tacrolimus (immunosuppressive medication used, among others, in the treatment of atopic dermatitis): concomitant use of NSAIDs with tacrolimus may increase the risk of nephrotoxic effects;
• lithium preparations, digoxin, ketoconazole: ARTHROTEC may increase the plasma levels of lithium and digoxin at steady state and decrease the plasma level of ketoconazole;
• oral antidiabetic medications: NSAIDs may enhance the effect of oral antidiabetic medications. When taken concomitantly with oral antidiabetic medications, the risk of hypoglycemia or hyperglycemia may occur;
• anticoagulant medications, such as warfarin, and antiplatelet agents, such as acetylsalicylic acid. Concomitant use of ARTHROTEC with acetylsalicylic acid is not recommended;
• selective serotonin reuptake inhibitors (some medications used in the treatment of depression): NSAIDs may enhance the effect of these medications, thereby increasing the risk of gastrointestinal bleeding;
• methotrexate: NSAIDs may increase the toxicity of methotrexate associated with its increased plasma level, especially in patients receiving high doses of methotrexate;
• other NSAIDs and corticosteroids: concomitant use of these medications with ARTHROTEC may increase the frequency of ulcers or gastrointestinal bleeding and other side effects;
• antihypertensive medications, including diuretics, ACE inhibitors, angiotensin II receptor antagonists, and beta-blockers: NSAIDs may reduce their effectiveness. In patients with impaired renal function (e.g., dehydrated or elderly patients with impaired renal function), concomitant use of an ACE inhibitor or an angiotensin II receptor antagonist and/or diuretics with a cyclooxygenase inhibitor may lead to renal impairment, including acute renal failure, which is usually reversible;
• medications that neutralize stomach acid: these medications may delay the absorption of diclofenac. Medications that neutralize stomach acid containing magnesium may enhance the diarrhea caused by misoprostol;
• quinolones: in patients taking NSAIDs and quinolones, there may be an increased risk of seizures;
• mifepristone (a non-contraceptive abortion medication not available in Poland): NSAIDs may reduce its effectiveness. NSAIDs should be used after 8 to 12 days after administration of mifepristone;
• voriconazole (an antifungal medication);
• sulfinpyrazone (a medication used in the treatment of gout).

ARTHROTEC with food and drink

Tablets should be taken during meals.

Pregnancy, breastfeeding, and fertility

Pregnancy
The patient should not take ARTHROTEC if they are pregnant, suspect they may be pregnant, or are trying to become pregnant. The patient should inform their doctor about planned pregnancy.
Due to the potential risk to the fetus, before starting treatment with this medicine, the patient must ensure they are not pregnant. Women of childbearing age, during treatment with this medicine, must use effective contraception.
The doctor must inform the patient about the risks associated with becoming pregnant while taking ARTHROTEC, as the medicine may cause miscarriage, premature birth, or fetal malformation (congenital defects). If the patient is pregnant, they should never take this medicine, as it may have a serious impact on the child, especially on their heart, lungs, and/or kidneys, up to causing death. If the patient has taken this medicine during pregnancy, they should discuss it with their doctor. If the patient decides to continue the pregnancy, they should be closely monitored by ultrasound, with particular attention to the evaluation of the fetus's limbs and head.
Diclofenac may cause premature closure of the ductus arteriosus.
NSAIDs used in the second or third trimester of pregnancy may cause renal impairment in the fetus, which may contribute to a decrease in the amount of amniotic fluid or, in severe cases, to oligohydramnios. These effects may occur soon after starting treatment and are usually reversible. The amount of amniotic fluid should be closely monitored in pregnant women taking NSAIDs.
Breastfeeding
If the patient is breastfeeding, they should consult their doctor or pharmacist before taking this medicine. ARTHROTEC should not be used during breastfeeding. Misoprostol is metabolized to misoprostolic acid, which passes into breast milk and may cause adverse effects in breastfed infants, such as diarrhea.

Driving and using machines

Patients who experience dizziness or other central nervous system disorders while taking NSAIDs should not drive vehicles or operate machinery.

ARTHROTEC contains lactose monohydrate

If the patient has previously been diagnosed with intolerance to some sugars, they should consult their doctor before taking the medicine.

ARTHROTEC contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means the medicine is considered "sodium-free".

ARTHROTEC contains hydrogenated castor oil

The medicine contains hydrogenated castor oil, which may cause gastrointestinal upset and diarrhea.

3. How to take ARTHROTEC

This medicine should always be taken as directed by the doctor. In case of doubts, the patient should consult their doctor or pharmacist.
Tablets should be swallowed whole, without chewing.

Adults

The recommended dose is one tablet taken during meals, one to three times a day.

Use in the elderly

No dose adjustment is necessary, but patients should be closely monitored.

Use in patients with renal impairment

No dose adjustment is necessary in patients with mild or moderate renal impairment, but they should be closely monitored.

Use in patients with hepatic impairment

No dose adjustment is necessary in patients with mild or moderate hepatic impairment, but they should be closely monitored.

Use in children and adolescents

The safety and efficacy of ARTHROTEC in children and adolescents under 18 years of age have not been established.

Overdose of ARTHROTEC

In case of overdose, the patient should contact their doctor or pharmacist.
Treatment of acute NSAID overdose consists of supportive and symptomatic measures. It is recommended to take actions to reduce the absorption of the recently taken medicine, such as administering activated charcoal.
Clinical symptoms that may indicate misoprostol overdose include: sedation, tremors, seizures, dyspnea, abdominal pain, diarrhea, fever, tachycardia or bradycardia (slow heart rate).

Missed dose of ARTHROTEC

The patient should not take a double dose to make up for a missed dose.

Discontinuation of ARTHROTEC

The decision to discontinue treatment is made by the doctor. If the patient feels that the effect of the medicine is too strong or too weak, they should contact their doctor.
In case of any further doubts about the use of this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, ARTHROTEC can cause side effects, although not everybody gets them.

If the patient experiences any of the following symptoms, they should stop taking ARTHROTEC and seek medical attention immediately:

ARTHROTEC and seek medical attention immediately:

• weakness or inability to move one side of the body, slurred speech (stroke)* or chest pain (heart attack)*, or heart failure* - occur uncommonly
• shortness of breath* - occur uncommonly
• infections with symptoms such as chills*, fever* - occur uncommonly
• severe abdominal pain or any symptoms of gastrointestinal bleeding* (occur uncommonly), or perforation* (frequency of occurrence is unknown), such as black or bloody stools, or vomiting blood
• severe allergic reaction, such as skin rash, facial swelling, wheezing, or difficulty breathing [anaphylactic reaction (anaphylactic shock)]*, or angioedema* - occur rarely
• jaundice (yellowing of the skin or whites of the eyes)* - frequency of occurrence is unknown
• decreased platelet count (increased risk of bleeding or bruising)* - occur uncommonly
• symptoms of meningitis [stiff neck, headache, nausea (vomiting), vomiting, fever, or altered consciousness]* - frequency of occurrence is unknown
• chest pain, which may be a symptom of a potentially severe allergic reaction called Kounis syndrome - frequency of occurrence is unknown
• severe skin reaction, such as rash, blistering (e.g., on the mucous membranes of the mouth and genital organs) or peeling of the skin (DRESS syndrome, Stevens-Johnson syndrome*, toxic epidermal necrolysis*, erythema multiforme*, and other skin reactions) - frequency of occurrence is unknown

Frequency not known(cannot be estimated from available data)

• hemolytic anemia*, agranulocytosis*, platelet aggregation inhibition*
• fluid retention*
• mood changes*
• vasculitis*
• liver failure*
• mucocutaneous reactions*
• renal failure*, renal impairment*, renal papillary necrosis*, nephrotic syndrome*, interstitial nephritis*, membranous nephropathy*, focal segmental glomerulosclerosis*, other nephropathies*
• fetal death*, amniotic fluid embolism*, incomplete abortion*, premature birth*, abnormal uterine contractions*, placental retention or fetal membranes*
• severe uterine bleeding (uterine hemorrhage)*, uterine contractions, female infertility (reduced fertility in women)*
• uterine rupture*, uterine perforation* * Adverse reactions reported after the marketing authorization of the medicine. Adverse reactions from controlled clinical trials, lasting up to 24 months, mainly concern the gastrointestinal system. Diarrhea and abdominal pain are usually mild or moderate in severity and are transient; these symptoms occur early in the treatment phase and may last for several days. Diarrhea and abdominal pain usually resolve spontaneously during ARTHROTEC treatment. During treatment with NSAIDs, in very rare cases, exacerbation of infection-related conditions has been observed. After the marketing authorization of the medicine, the most frequently reported adverse reactions were gastrointestinal disorders (about 45% of all reported cases), followed by skin reactions and hypersensitivity, which is consistent with the adverse reaction profile of NSAIDs. The use of diclofenac, especially in high doses (150 mg per day) and long-term treatment, may be associated with a slightly increased risk of serious arterial thrombotic events (e.g., myocardial infarction or stroke).

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store ARTHROTEC

The medicine should be stored out of sight and reach of children.
Do not store above 25°C. Store in the original packaging to protect from moisture.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What ARTHROTEC contains

• The active substances of ARTHROTEC are diclofenac and misoprostol. Each tablet consists of a core resistant to gastric juice, containing 50 mg of diclofenac sodium, coated with an outer layer containing 0.2 mg of misoprostol.
• Other ingredients are: lactose monohydrate, microcrystalline cellulose, cornstarch, povidone K 30, magnesium stearate, methacrylic acid copolymer (type C), sodium hydroxide (see section 2 "ARTHROTEC contains sodium"), triethyl citrate, crospovidone, colloidal anhydrous silica, hydrogenated castor oil (see section 2 "ARTHROTEC contains hydrogenated castor oil"), talc.

What ARTHROTEC looks like and contents of the pack

White, round, biconvex tablets, marked "A" on one side and "Searle 1411" on the other side.
The packaging contains: 10 tablets (1 blister), 20 tablets (2 blisters of 10 tablets), 30 tablets (3 blisters of 10 tablets), or 60 tablets (6 blisters of 10 tablets).
Outer packaging: cardboard box.
For more detailed information, the patient should contact the marketing authorization holder or parallel importer.

Marketing authorization holder in Portugal, the country of export:

Laboratórios Pfizer, Lda.
Lagoas Park
Edifício 10
2740-271 Porto Salvo
Portugal

Manufacturer:

Piramal Pharma Solutions (Dutch) B.V.
Level, 7e verdieping
Bargelaan 200
2333 CW, Leiden
Netherlands

Parallel importer:

InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw

Repackaged by:

InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Marketing authorization number in Portugal, the country of export:4632782
8786202
4632881
8786210
Parallel import authorization number:439/15

Date of leaflet approval: 01.07.2025

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