Arthrotec Forte

Package Leaflet: Information for the Patient

ARTHROTEC Forte, 75 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.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

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

1. What is ARTHROTEC Forte and what is it used for

ARTHROTEC Forte is a nonsteroidal anti-inflammatory drug (NSAID).
ARTHROTEC Forte is indicated for use in patients who require concomitant treatment with a nonsteroidal anti-inflammatory drug (diclofenac) and misoprostol.
Diclofenac in ARTHROTEC Forte 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 Forte

When not to take ARTHROTEC Forte

• if you are 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, but are not limited to, 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 you are of childbearing age and do not use effective contraception to prevent pregnancy (for additional information, see "Pregnancy");
• in patients in whom NSAIDs cause asthma attacks, urticaria, or acute rhinitis;
• for the treatment of post-operative pain following coronary artery bypass grafting;
• if you have heart disease and/or cerebrovascular disease, such as moderate or severe heart failure, myocardial infarction, stroke, transient cerebral ischemia, or cerebral vascular thrombosis, or after revascularization or coronary artery bypass grafting;
• if you have had circulatory disorders (peripheral vascular disease);
• in patients with severe renal or hepatic impairment.

Warnings and precautions

Before starting treatment with ARTHROTEC Forte, discuss it with your doctor or pharmacist.
If you are pregnant or planning to become pregnant (see "Pregnancy"), due to the risk to the fetus, treatment with ARTHROTEC Forte should be discontinued immediately;

• you are of childbearing age (see "Pregnancy"); due to the risk to the fetus, it is essential to use effective contraception during treatment with this medicine.

Special warnings when taking ARTHROTEC Forte

• in patients with renal, hepatic, or severe heart disorders, as well as in the elderly. In cases of severe hepatic impairment, significant dehydration, ARTHROTEC Forte should only be used in exceptional circumstances and under close monitoring of the patient's condition (see "When not to take ARTHROTEC Forte");
• 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 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 combination drug containing diclofenac and misoprostol;
• in patients with bleeding or coagulation disorders, or with a history of cerebrovascular hemorrhage, as NSAIDs, including ARTHROTEC Forte, may reduce platelet aggregation and prolong bleeding time;
• in patients taking anticoagulant medications, such as 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 Forte 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 Forte 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 Forte, tell your doctor if you have recently undergone or are scheduled to undergo stomach or gastrointestinal surgery, as ARTHROTEC Forte may sometimes cause impaired wound healing in the intestines after surgery.
ARTHROTEC Forte 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 the medicine 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 Forte 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 a history of gastrointestinal diseases, active or in the past, such as ulcers, gastrointestinal bleeding, or inflammation of the gastrointestinal mucosa.
Therefore, ARTHROTEC Forte should be used with caution in these patients, starting treatment with the lowest effective dose.
ARTHROTEC Forte should not be used in women of childbearing age, unless the patient uses effective methods of contraception and has been informed of the risks associated with the use of the medicine during pregnancy. The packaging includes a warning: "Do not use in women of childbearing age, unless they use effective methods of contraception".
Taking such medications as ARTHROTEC Forte 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.
During treatment with NSAIDs, including the combination drug containing diclofenac and misoprostol, very rare severe skin reactions have been observed. The patient should immediately report any skin changes to the treating doctor. The doctor may decide to discontinue treatment with ARTHROTEC Forte in case of the first occurrence of skin rash, mucosal lesions, or any other symptoms of hypersensitivity.
In patients with systemic lupus erythematosus and connective tissue diseases, ARTHROTEC Forte may increase the risk of developing aseptic meningitis.
During long-term treatment with high doses of pain and/or anti-inflammatory medications, headache may occur, which should not be treated by administering further doses of the medicine or other NSAIDs.
ARTHROTEC Forte may mask fever and thus the underlying disease.
The medicine may impair fertility. If the patient plans to become pregnant or has difficulty becoming pregnant, she should inform her doctor.
ARTHROTEC Forte may cause vision disturbances. In case of vision disturbances, contact an ophthalmologist.
Before taking the medicine, tell your doctor:

• if you smoke
• if you have diabetes
• if you have angina pectoris, thrombosis, hypertension, elevated cholesterol, or elevated 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 Forte and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or plan to take.
Tell your doctor if you are taking any of the following medicines:

• diuretics (diuretics): NSAIDs may reduce the effectiveness of diuretics. When taking diuretics that spare potassium, hyperkalemia may occur;
• cyclosporine (immunosuppressive drugs used, among others, in the treatment of transplant patients): diclofenac may increase the nephrotoxicity of cyclosporine; it is essential to start treatment with ARTHROTEC Forte at the lowest dose and closely monitor the patient's condition for signs of toxic effects;
• tacrolimus (immunosuppressive drug used, among others, in the treatment of atopic dermatitis): when taking NSAIDs with tacrolimus, there is a possible increased risk of nephrotoxic effects;
• lithium preparations, digoxin, ketoconazole: ARTHROTEC Forte may increase the plasma levels of lithium and digoxin at steady state and decrease the plasma level of ketoconazole;
• oral antidiabetic drugs: NSAIDs may enhance the effect of oral antidiabetic drugs. When taken concomitantly with oral antidiabetic drugs, 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 Forte with acetylsalicylic acid is not recommended;
• selective serotonin reuptake inhibitors (some antidepressant medications): 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 Forte may increase the frequency of ulcers and 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 administration of an ACE inhibitor or an angiotensin II receptor antagonist and/or a diuretic with a cyclooxygenase inhibitor may lead to renal impairment, including acute renal failure, which is usually reversible;
• medicines that neutralize stomach acid: these medicines may delay the absorption of diclofenac. Medicines 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, not available in Poland): NSAIDs may reduce its effect. NSAIDs should be used after 8 to 12 days from mifepristone administration;
• voriconazole (an antifungal medication);
• sulfinpyrazone (a medication used to treat gout).

ARTHROTEC Forte with food and drink

Tablets should be taken with food.

Pregnancy, breastfeeding, and fertility

Pregnancy
The patient should not take ARTHROTEC Forte if she is pregnant, thinks she may be pregnant, or is planning to become pregnant. The patient should inform her doctor if she is planning to have a child. Due to the potential risk to the fetus, before starting treatment with this medicine, the patient must ensure that she is not pregnant. Women who have not yet reached menopause, 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 Forte, as this medicine may cause miscarriage, premature birth, or fetal malformations (birth defects). If the patient is pregnant, she should NEVER take this medicine, as it may have a serious impact on the child, especially on its heart, lungs, and/or kidneys, up to causing death. If the patient has taken this medicine during pregnancy, she should discuss it with her doctor. If the patient decides to continue the pregnancy, she 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 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, before taking this medicine, she should consult her doctor or pharmacist. Do not use ARTHROTEC Forte 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 Forte contains lactose monohydrate

If you have been diagnosed with an intolerance to some sugars, you should contact your doctor before taking the medicine.

ARTHROTEC Forte contains sodium

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

ARTHROTEC Forte contains hydrogenated castor oil

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

3. How to take ARTHROTEC Forte

This medicine should always be taken exactly as directed by your doctor. If you are unsure, ask your doctor or pharmacist.
Swallow the tablets whole, do not chew.

Adults

The recommended dose is one tablet taken with food, one to two 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 Forte

In case of overdose, contact your 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 medicine, such as administering activated charcoal.
Clinical symptoms that may indicate diclofenac overdose include: hypotension, acute renal failure, respiratory depression, and coma. Clinical symptoms that may indicate misoprostol overdose include: sedation, tremors, seizures, dyspnea, abdominal pain, diarrhea, fever, hypotension, or bradycardia (slow heart rate).

Missed dose of ARTHROTEC Forte

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

Discontinuation of ARTHROTEC Forte

The decision to discontinue treatment is made by the doctor. If you feel that the effect of the medicine is too strong or too weak, contact your doctor.
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

If you experience any of the following symptoms, stop taking ARTHROTEC Forte 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
• decreased 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 serious 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

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

• abdominal pain, diarrhea, nausea, indigestion

Common(may affect up to 1 in 10 people)

• insomnia
• headache, dizziness
• duodenal ulcer, gastritis, esophagitis, gastrointestinal disorder*, vomiting, constipation, flatulence, eructation
• 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 developmental disorders*

Uncommon(may affect up to 1 in 100 people)

• vaginitis
• blurred vision*
• hypertension*
• stomatitis*
• urticaria*, purpura
• irregular or intermenstrual bleeding, menorrhagia, metrorrhagia (including postmenopausal bleeding), menstrual disorders
• edema*
• increased aspartate aminotransferase activity

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

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

Frequency not known(cannot be estimated from available data)

• hemolytic anemia*, agranulocytosis*, impaired platelet aggregation*
• fluid retention*
• mood changes*
• vasculitis*
• liver failure*, renal impairment*, renal papillary necrosis*, nephrotic syndrome*, interstitial nephritis*, membranous nephropathy*, focal segmental glomerulosclerosis*, nephritis*
• fetal death*, amniotic fluid embolism*, incomplete abortion*, premature birth*, abnormal uterine contractions*, placental retention or fetal membrane retention*
• abnormal uterine bleeding (metrorrhagia)*, uterine contractions, female infertility (reduced fertility in women)*
• uterine rupture*, uterine perforation*

* Side effects reported after the medicine was placed on the market.
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 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 treatment with ARTHROTEC Forte.
During treatment with NSAIDs, including the combination drug containing diclofenac and misoprostol, very rare severe skin reactions have been observed. The patient should immediately report any skin changes to the treating doctor. The doctor may decide to discontinue treatment with ARTHROTEC Forte in case of the first occurrence of skin rash, mucosal lesions, or any other symptoms of hypersensitivity.
After the medicine was placed on the market, the most frequently reported side effects were gastrointestinal disorders (about 45% of all reported cases), followed by skin reactions and hypersensitivity, which is consistent with the side effect profile of NSAIDs.
Taking high doses of diclofenac, especially 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 you experience any side effects, including those not listed in this leaflet, tell your 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
Jerozolimskie Avenue 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 to gather more information on the safety of the medicine.

5. How to store ARTHROTEC Forte

Keep the medicine out of the sight and reach of children.
Store in a temperature below 25°C.
Do not use this medicine after the expiry date stated on the carton after (EXP). The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. Ask your 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 Forte contains

• The active substances of the medicine are diclofenac and misoprostol. Each tablet consists of a core that is resistant to gastric juice, containing 75 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 section 2 "ARTHROTEC Forte contains lactose monohydrate"), microcrystalline cellulose, cornstarch, povidone, magnesium stearate, methacrylic acid copolymer (type C), sodium hydroxide (to adjust pH) (see section 2 "ARTHROTEC Forte contains sodium"), triethyl citrate, crospovidone, colloidal anhydrous silica, hydrogenated castor oil (see section 2 "ARTHROTEC Forte contains hydrogenated castor oil"), talc.

What ARTHROTEC Forte looks like and contents of the pack

White, round, biconvex tablets, marked "A" and "75" on one side and "Searle 1421" on the other side.
The pack contains: 10 tablets (1 blister) or 20 tablets (2 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, 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-arthrotecforte and on the website of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products http://www.urpl.gov.pl.