Arthrotec

Package Leaflet: Information for the Patient

ARTHROTEC, 50 mg + 0.2 mg, tablets

Diclofenac sodium + Misoprostol

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm them, even if their symptoms are the same as yours.
• 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 treatment with 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 prevention of gastric and/or duodenal ulcers in patients who require treatment with 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, perforation, or bleeding;
• in case of other active bleeding, such as cerebral hemorrhage;
• 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, hives, or acute rhinitis;
• for the treatment of post-operative pain in coronary artery bypass grafting;
• if the patient has heart disease and/or cerebrovascular disease, such as moderate or severe heart failure, myocardial infarction, stroke, transient ischemic attack (TIA), or cerebral vascular thrombosis, or after revascularization or coronary artery bypass grafting;
• if the patient has 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 planning to become pregnant (see the section on "Pregnancy"); due to the risk to the fetus, ARTHROTEC should be discontinued 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 precautions 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 circumstances and under close monitoring of the patient's condition (see the section "When not to take ARTHROTEC");
• when using diclofenac in high doses (150 mg per day) and in long-term treatment, as this may be associated with an increased risk of serious 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 ulcers 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 diclofenac and misoprostol medication;
• in patients with bleeding or blood clotting disorders, or with a history of cerebral hemorrhage, 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 may cause fluid retention and edema in this patient population. The doctor will provide the patient with information on monitoring and other special recommendations.

Avoid concomitant use of ARTHROTEC and other systemically administered NSAIDs, except for acetylsalicylic acid, including selective COX-2 inhibitors (e.g., rofecoxib, celecoxib), due to the increased frequency of ulcers and gastrointestinal 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 after surgical procedures.
ARTHROTEC may cause serious gastrointestinal side effects, including inflammation, bleeding, ulcers, and perforations of the stomach, small intestine, and large intestine, which can be fatal. If gastrointestinal bleeding or ulcers occur, the medication should be discontinued. These events can 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 medication, elderly patients, patients with cardiovascular disorders, patients taking concomitant acetylsalicylic acid, corticosteroids, selective serotonin reuptake inhibitors, patients consuming alcohol, or patients with a history of gastrointestinal diseases, active or inactive, 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 contraceptive methods and have been informed about the risks associated with taking the medication during pregnancy. The packaging includes a warning: "Do not use in women of childbearing age unless they use effective contraception".
Taking medications like 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 medication. Do not use higher doses or longer treatment than recommended.
During treatment with NSAIDs, including the combined diclofenac and misoprostol medication, very rare severe skin reactions have been observed. 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 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 additional doses of the medication or other NSAIDs.
ARTHROTEC may mask fever, and thus the underlying disease.
The medication 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 eye doctor.
Before taking the medication, the patient should inform their doctor:

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

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

ARTHROTEC and other medications

The patient should tell their doctor or pharmacist about all medications they are currently taking or have recently taken, as well as any medications 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 diuretics that spare potassium, 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): when using NSAIDs concomitantly with tacrolimus, there is a possible increased risk of nephrotoxic effects;
• lithium preparations, digoxin, ketoconazole: ARTHROTEC may increase the levels of lithium and digoxin in the blood at steady state and decrease the levels of ketoconazole;
• oral antidiabetic medications: NSAIDs may enhance the effects of oral antidiabetic medications. When used concomitantly with oral antidiabetic medications, there may be a risk of hypoglycemia or hyperglycemia;
• anticoagulant medications, such as warfarin, and platelet aggregation inhibitors, 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 effects of these medications, thereby increasing the risk of gastrointestinal bleeding;
• methotrexate: NSAIDs may increase the toxicity of methotrexate associated with its increased blood levels, particularly 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 (AIIA), 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 ACE inhibitors or AIIA medications 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 in gastric juice, 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-steroidal anti-progestogen medication, not available in Poland): NSAIDs may reduce its effectiveness. NSAIDs should be used after 8 to 12 days from mifepristone administration;
• voriconazole (an antifungal medication);
• sulfinpyrazone (a medication used in the treatment of gout).

ARTHROTEC with food and drink

Tablets should be taken with food.

Pregnancy, breastfeeding, and fertility

Pregnancy
The patient should not take ARTHROTEC if they are pregnant, think they may be pregnant, or are trying to become pregnant. The patient should inform their doctor if they plan to have a child. Due to the potential risk to the fetus, the patient must ensure they are not pregnant before starting treatment with this medication. Women who have not yet reached menopause and are taking this medication must use effective contraception. The doctor must inform the patient about the risks associated with becoming pregnant while taking ARTHROTEC, as the medication may cause miscarriage, premature birth, or fetal malformation (birth defects). If the patient is pregnant, they should never take this medication, as it may have a serious impact on the child, particularly on their heart, lungs, and/or kidneys, up to causing death. If the patient has taken this medication during pregnancy, they should discuss it with their doctor. If the patient decides to continue the pregnancy, they should be closely monitored using 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 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 medication. Do not use ARTHROTEC 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 been diagnosed with intolerance to some sugars, they should consult their doctor before taking the medication.

ARTHROTEC contains sodium

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

ARTHROTEC contains hydrogenated castor oil

The medication contains hydrogenated castor oil, which may cause nausea and diarrhea.

3. How to take ARTHROTEC

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

Adults

The recommended dose is one tablet taken with food, 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

Safety and efficacy 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 treatment. It is recommended to take measures to reduce the absorption of the recently taken medication, such as administering activated charcoal.
Clinical symptoms that may indicate diclofenac overdose include: sedation, tremors, convulsions, dyspnea, abdominal pain, diarrhea, fever, tachycardia, or hypotension or bradycardia (slow heart rate).

Missed dose of ARTHROTEC

A double dose should not be taken 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 medication is too strong or too weak, they should consult their doctor.
In case of any further doubts about the use of this medication, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medications, 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:

• 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* - occurs 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
• reduced platelet count (increased risk of bleeding or bruising)* - occurs 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 genitals) or peeling of the skin (DRESS syndrome, Stevens-Johnson syndrome*, toxic epidermal necrolysis*, and erythema multiforme*) - frequency of occurrence is unknown

Other side effects
Very common(may occur in more than 1 in 10 people)

• abdominal pain, diarrhea, nausea, indigestion

Common(may occur in up to 1 in 10 people)

• insomnia
• headache, dizziness
• gastric ulcer, duodenal ulcer, gastritis, esophagitis, gastrointestinal inflammation*, vomiting, constipation, bloating with gas, belching
• skin rash*, itching
• increased alanine aminotransferase activity, decreased red blood cell count in blood tests (decreased hematocrit value), increased alkaline phosphatase activity in blood
• fetal development abnormalities*

Uncommon(may occur in up to 1 in 100 people)

• vaginitis
• blurred vision*
• hypertension*
• stomatitis*
• hives*, purpura
• irregular or intermenstrual bleeding, menorrhagia, metrorrhagia, menstrual disorders
• edema*
• increased aspartate aminotransferase activity

Rare(may occur in up to 1 in 1,000 people)

• nightmares*
• pancreatitis*
• hepatitis*
• skin blisters (bullous dermatitis)*
• chest pain, dysmenorrhea

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*, nephropathy*
• fetal death*, amniotic fluid embolism*, incomplete abortion*, premature birth*, abnormal uterine contractions*, placental retention or fetal membrane rupture*
• severe menstrual bleeding (metrorrhagia)*, uterine contractions, female infertility (reduced fertility in women)*
• uterine rupture*, uterine perforation*

* Side effects reported after the medication was approved.
Side effects from controlled clinical trials, lasting up to 24 months, mainly concern the gastrointestinal system. Diarrhea and abdominal pain are usually mild or moderate 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 treatment with ARTHROTEC.
During treatment with NSAIDs, including the combined diclofenac and misoprostol medication, very rare severe skin reactions have been observed. 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.
After the medication was approved, the most frequently reported side effects were gastrointestinal side effects (about 45% of all reported cases), followed by skin reactions and hypersensitivity, which is consistent with the side effect profile of NSAIDs.
The use of diclofenac, especially in high doses (150 mg per day) and in 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 side effects occur, including any side effects not listed in this leaflet, the patient should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder or its representative.
Reporting side effects will help gather more information on the safety of the medication.

5. How to store ARTHROTEC

The medication should be stored out of sight and reach of children.
Store in a dry place at a temperature below 25°C.
Do not use this medication after the expiration date stated on the packaging (EXP). The expiration date refers to the last day of the month.
Medications should not be disposed of in wastewater or household waste. The patient should ask their pharmacist how to dispose of unused medications. This will help protect the environment.

6. Contents of the pack and other information

What ARTHROTEC contains

• The active substances of the medication 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 (in the form of a suspension of Misoprostol: Hypromellose 1:100).
• Other ingredients are: lactose monohydrate (see the section "ARTHROTEC contains lactose monohydrate"), microcrystalline cellulose, cornstarch, povidone, magnesium stearate, methacrylic acid copolymer (type C), sodium hydroxide (to adjust pH) (see the section "ARTHROTEC contains sodium"), triethyl citrate, crospovidone, colloidal anhydrous silica, hydrogenated castor oil (see the section "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

Marketing authorization holder

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Importer

Piramal Pharma Solutions (Dutch) B.V.
Bargelaan 200
2333 CW
Leiden
Netherlands
To obtain more detailed information, please contact the local representative of the marketing authorization holder:
Pfizer Polska Sp. z o.o.; phone: 22 335 61 00
Date of last revision of the leaflet:07/2024
Detailed and up-to-date information about this product can be obtained by scanning the QR code on the outer packaging using a mobile device. The same information is also available at the URL: https://pfi.sr/ulotka-arthrotec and on the website of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
http://www.urpl.gov.pl.