Arthrotec Forte

LEAFLET INCLUDED IN THE PACKAGING: INFORMATION FOR THE USER

Warning! Keep the leaflet, the information on the immediate packaging is in a foreign language!

Arthrotec Forte (Arthrotec 75 mg/0.2 mg)

75 mg + 0.2 mg, enteric-coated tablets

Diclofenac sodium + Misoprostol
Arthrotec Forte and Arthrotec 75 mg/0.2 mg are different trade names for the same medicine.

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

• You should keep the 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 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 packaging and other information

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

Arthrotec Forte is a non-steroidal anti-inflammatory medicine (NSAID).
Arthrotec Forte is indicated for use in patients who require concomitant use of a non-steroidal 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 treatment of patients who require gastric and/or duodenal ulcer prevention caused by the use of NSAIDs.

2. Important information before taking Arthrotec Forte

When not to take Arthrotec Forte

• during pregnancy or in women planning to become pregnant;
• in patients who have experienced asthma attacks, hives, or acute rhinitis caused by NSAIDs;
• for the treatment of post-operative pain in coronary artery bypass grafting;
• in patients with severe renal or hepatic impairment.

Warnings and precautions

Before starting to take Arthrotec Forte, you should discuss it with your doctor or pharmacist.
If the patient:

• is pregnant or plans to become pregnant (see the "Pregnancy" section); due to the risk to the fetus, taking Arthrotec Forte should be stopped immediately.
• is of childbearing age (see the "Pregnancy" section); due to the risk to the fetus, it is essential to use effective contraception while taking this medicine.

Special caution 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 cases and under close monitoring of the patient's condition (see the "When not to take Arthrotec Forte" section);
• when using 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 affecting the arteries (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 diclofenac and misoprostol medication;
• in patients with bleeding or blood clotting disorders, as well as in patients with a history of cerebral vascular bleeding, as NSAIDs, including Arthrotec Forte, 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 Forte may exacerbate the 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.

You should 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, you should 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 perforations of the stomach, small intestine, and large intestine, which can be fatal. If gastrointestinal bleeding or ulcers occur, you should discontinue the medication. 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 the 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 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 premenopausal women unless they use effective contraceptive methods and have been informed about 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 medicines like Arthrotec Forte may be associated with a small increased risk of heart attack (myocardial infarction) or stroke. This risk increases with long-term use of high doses of the medicine. You should not use higher doses or longer treatment than recommended.
During the use of 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 Forte 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 Forte 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 medicine or other NSAIDs.
Arthrotec Forte 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 Forte may cause vision disturbances. In case of vision disturbances, the patient should contact an eye doctor.
Before taking the medicine, the patient should inform their doctor:

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

Arthrotec Forte and other medicines

The patient should inform their doctor if they are taking any of the following medicines:

• diuretics (diuretic medicines): NSAIDs may reduce the effectiveness of diuretics. During concomitant use of potassium-sparing diuretics, an increase in potassium levels in the blood may occur;
• cyclosporine (immunosuppressive medicines used, among others, in the treatment of transplant patients): diclofenac may increase the nephrotoxicity of cyclosporine; it is essential to start taking Arthrotec Forte with the lowest dose and closely monitor the patient's condition for signs of toxic effects;
• tacrolimus (an immunosuppressive medicine 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 Forte may increase the levels of lithium and digoxin in the blood at steady state and decrease the levels of ketoconazole;
• antidiabetic medicines: NSAIDs may enhance the effect of oral antidiabetic medicines. During concomitant administration with antidiabetic medicines, the risk of hypoglycemia or hyperglycemia may occur;
• anticoagulant medicines, such as warfarin, and antiplatelet agents, such as acetylsalicylic acid. Concomitant use of Arthrotec Forte with acetylsalicylic acid is not recommended;
• selective serotonin reuptake inhibitors (some medicines used in the treatment of depression): NSAIDs may enhance the effect of these medicines, thereby increasing the risk of gastrointestinal bleeding;
• methotrexate: NSAIDs may increase the toxicity of methotrexate associated with its increased levels in the blood, especially in patients receiving high doses of methotrexate;
• other NSAIDs and corticosteroids: concomitant use of these medicines with Arthrotec Forte may increase the frequency of ulcers or gastrointestinal bleeding and other side effects;
• antihypertensive medicines, 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;
• medicines that neutralize stomach acid: these medicines may delay the absorption of diclofenac. Medicines 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-steroidal anti-progestogen medicine, not available in Poland): NSAIDs may reduce its effectiveness. NSAIDs should be used after 8 to 12 days from mifepristone administration;
• voriconazole (an antifungal medicine);
• sulfinpyrazone (a medicine used in the treatment of gout).

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.

Arthrotec Forte with food and drink

Tablets should be taken during meals.

Pregnancy, breastfeeding, and fertility

Pregnancy
The patient should not take Arthrotec Forte if they are pregnant, think 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 to take this medicine, the patient must ensure they are not pregnant. Women of childbearing age, during the use of this medicine, must use effective contraception.
The doctor must inform the patient about the risks associated with becoming pregnant while taking Arthrotec Forte, as the medicine may cause miscarriage, premature birth, or fetal malformation (birth 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 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 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 Forte should not be used during breastfeeding. Misoprostol is metabolized to misoprostolic acid, which passes into breast milk and may cause side 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 the patient has previously been diagnosed with intolerance to some sugars, they should consult their doctor before taking the medicine.

Arthrotec Forte contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means 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 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 two times a day.

Use in the elderly

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

Use in patients with renal impairment

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

Use in patients with hepatic impairment

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

Use in children and adolescents

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

Overdose of Arthrotec Forte

In case of overdose, the patient should consult their doctor or pharmacist.
Treatment of acute NSAID poisoning consists of supportive and symptomatic treatment. It is recommended to take measures to reduce the absorption of the recently taken medicine, such as inducing vomiting, gastric lavage, or 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). Inducing diuresis (urine excretion) may be beneficial, as the metabolites of Arthrotec Forte are excreted in the urine.

Missed dose of Arthrotec Forte

The patient should 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 the patient feels that the effect of the medicine is too strong or too weak, they should consult 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, this medicine can cause side effects, although not everybody gets them.
Very common (occurring in more than 1 in 10 patients)

• abdominal pain, diarrhea, nausea, dyspepsia.

Common (occurring in more than 1 in 100 and less than 1 in 10 patients)

• insomnia
• headache, dizziness
• gastric and/or duodenal ulcer, gastritis, esophagitis, gastrointestinal inflammation, vomiting, constipation, bloating with gas, belching
• rash, itching
• increased alanine aminotransferase activity, decreased hematocrit value, increased alkaline phosphatase activity in the blood
• fetal malformation.

Uncommon (occurring in more than 1 in 1000 and less than 1 in 100 patients)

• vaginitis
• thrombocytopenia (low platelet count)
• stroke
• blurred vision
• myocardial infarction, heart failure
• hypertension
• dyspnea
• gastrointestinal bleeding, oral mucosal inflammation
• urticaria, erythema multiforme
• irregular or intermenstrual bleeding, menorrhagia, vaginal bleeding (including postmenopausal bleeding), menstrual disorders
• fever, edema, chills
• increased aspartate aminotransferase activity.

Rare (occurring in less than 1 in 1000 patients)

• anaphylactic reaction
• nightmares
• pancreatitis
• hepatitis
• bullous skin eruption, angioedema
• chest pain, dysmenorrhea.

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

• hemolytic anemia, agranulocytosis, platelet aggregation inhibition
• fluid retention
• mood changes
• aseptic meningitis (characterized by symptoms such as neck stiffness, headache, nausea, vomiting, fever, or altered consciousness)
• vasculitis
• gastrointestinal perforation
• liver failure, jaundice
• toxic epidermal necrolysis, Stevens-Johnson syndrome (mucosal and genital lesions), erythema multiforme, exfoliative dermatitis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome)
• renal failure, renal impairment, renal papillary necrosis, nephrotic syndrome, interstitial nephritis, membranous glomerulonephritis, focal glomerulonephritis
• fetal death, amniotic fluid embolism, incomplete abortion, premature birth, abnormal uterine contractions, placental retention or fetal membrane retention
• uterine bleeding, uterine contractions, female infertility (reduced fertility)
• uterine rupture, uterine perforation.

*Side effects reported after the medicine was placed on the market.
The patient should immediately tell their doctor if they experience chest pain, which may be a symptom of a potentially serious allergic reaction called Kounis syndrome.
Side effects from controlled clinical trials, lasting up to 24 months, mainly affect 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 the use of NSAIDs, very rare cases of exacerbation of infection-related inflammation have been observed.
After the medicine was placed on the market, 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 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 the leaflet, the patient should tell 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, 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 Forte

The medicine should be stored out of sight and reach of children.
Store in a temperature below 25°C in the original packaging.
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 packaging and other information

What Arthrotec Forte contains

• The active substances of the medicine are diclofenac and misoprostol. Each enteric-coated tablet consists of a core 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 dispersion of Misoprostol: Hypromellose 3 mPas, 1:100).
• Other ingredients are: lactose monohydrate, microcrystalline cellulose, corn starch, povidone K 30, magnesium stearate, methacrylic acid copolymer (type C), sodium hydroxide (for pH adjustment) (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 packaging

White, round, biconvex tablets, marked "A" and "75" on one side and "Searle 1421" on the other side.
The packaging contains: 10 tablets (1 blister) or 20 tablets (2 blisters of 10 tablets).
Outer packaging: cardboard box.
For more detailed information, the patient should contact the marketing authorization holder or the parallel importer.

Marketing authorization holder in Romania, the country of export:

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

Manufacturer:

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

Parallel importer:

Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź

Repackaged by:

Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
CEFEA Sp. z o.o. Sp. komandytowa
ul. Działkowa 56
02-234 Warsaw
SHIRAZ PRODUCTIONS Sp. z o.o.
ul. Tymiankowa 24/28
95-054 Ksawerów
Marketing authorization number in Romania, the country of export: 12398/2019/01
12398/2019/02
Parallel import authorization number: 249/23

Date of leaflet approval: 31.10.2023

[Information about the trademark]