Package leaflet: Information for the patient

Warning! Please keep this leaflet. The information on the immediate packaging is in a foreign language.
Arthrotec, 50 mg + 0.2 mg, tablets
Diclofenacum natricum + Misoprostolum
Please read this leaflet carefully before taking the medicine, as it contains important information for the patient.

Keep this leaflet for possible future reference.
If you have any doubts, please consult your doctor, pharmacist, or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
If you experience any adverse effects, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

What Arthrotec is and what it is used for
Important information before taking Arthrotec
How to take Arthrotec
Possible side effects
How to store Arthrotec
Contents of the pack and other information

1. What Arthrotec is and what it is used for

Arthrotec is a non-steroidal anti-inflammatory drug (NSAID).
Arthrotec is indicated for use in patients requiring concomitant administration of a non-steroidal anti-inflammatory drug (diclofenac) and misoprostol.
Diclofenac contained in Arthrotec is indicated for the symptomatic treatment of osteoarthritis and rheumatoid arthritis. Misoprostol is indicated for the treatment of patients in whom prophylaxis against gastric and/or duodenal ulceration induced by NSAIDs is required.

2. Important Information Before Using Arthrotec

When not to use 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). Symptoms of hypersensitivity include, among others, chest pain;
in case of active gastric or duodenal ulcer, perforation, or bleeding;
in case of any other active bleeding, e.g. cerebrovascular hemorrhage;
during pregnancy or in women planning pregnancy;
if the patient is of childbearing potential and is not using an effective method of contraception to prevent pregnancy (for additional information see section "Pregnancy");
in patients in whom NSAIDs have triggered asthma attacks, urticaria, or acute rhinitis;
for perioperative pain management in coronary artery bypass graft (CABG) surgery;
if the patient has heart disease and/or cerebrovascular disease, e.g. moderate or severe congestive heart failure, previous myocardial infarction, stroke, transient ischemic attack (TIA), or arterial embolism in the heart or brain, or following revascularization or bypass surgery of blocked vessels; Page 1 of 9
if the patient has current or previous circulatory disorders (peripheral vascular disease);
in patients with severe renal or hepatic impairment.

Warnings and precautions
Before starting treatment with Arthrotec, discuss this with your doctor or pharmacist.
If the patient:

is pregnant or planning to become pregnant (see section "Pregnacy"); due to the risk to the fetus, treatment with Arthrotec should be discontinued immediately.
is of childbearing potential (see section "Pregnancy"); due to the risk to the fetus, it is important to use an effective method of contraception during treatment.

Exercise special caution when using Arthrotec

in patients with impaired renal, hepatic, or serious cardiac function, and in elderly patients. In cases of severe hepatic impairment or significant dehydration, Arthrotec should only be used in exceptional circumstances and under strict monitoring of the patient's condition (see section "When not to use Arthrotec");
when using diclofenac at high doses (150 mg daily) or for 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 symptoms and/or signs of serious cardiovascular toxicity and actions to take if such symptoms occur;
in patients with a history of gastrointestinal toxicity or gastric and/or duodenal ulcer disease. In particular, elderly patients should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), especially during the initial phase of treatment. If gastrointestinal bleeding or ulceration occurs, the doctor will decide to discontinue treatment with the combination drug containing diclofenac and misoprostol;
in patients with hematopoietic system disorders or coagulation disorders, and in patients with a history of cerebrovascular hemorrhage, as Arthrotec, like other NSAIDs, may reduce platelet aggregation and prolong bleeding time;
in patients taking anticoagulants: warfarin and/or coumarin derivatives, and new oral anticoagulants (e.g. apixaban, dabigatran, rivaroxaban) due to increased risk of gastrointestinal bleeding and other hemorrhages;
in patients with ulcerative colitis or Crohn's disease, as Arthrotec may exacerbate symptoms of these conditions;
in patients with bronchial asthma or allergic disease, currently or in the past, as NSAIDs may cause bronchospasm in such patients;
in patients with hypertension and/or mild congestive heart failure, as fluid retention and edema have been observed with NSAID use in these patients. The doctor will provide information regarding monitoring and other special recommendations.

Concomitant use of Arthrotec and other systemically administered NSAIDs other than acetylsalicylic acid, including selective COX-2 inhibitors (e.g. rofecoxib, celecoxib), should be avoided due to increased frequency of gastrointestinal ulcers and bleeding.
Before using Arthrotec, inform the doctor if the patient has recently undergone or is scheduled for surgery of the stomach or gastrointestinal tract, as Arthrotec may occasionally impair intestinal wound healing after surgery.
Arthrotec may cause severe gastrointestinal adverse effects, including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, and large intestine, which may be fatal. If gastrointestinal bleeding or ulceration occurs, treatment should be discontinued. These events may occur at any time during treatment, with or without warning symptoms, or in patients with a history of severe gastrointestinal adverse events.
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Patients at highest risk of gastrointestinal complications associated with Arthrotec use include those receiving high doses, elderly patients, patients with cardiovascular disorders, those concurrently taking acetylsalicylic acid, corticosteroids, selective serotonin reuptake inhibitors (SSRIs), patients consuming alcohol, or those with active or past gastrointestinal diseases such as ulceration, gastrointestinal bleeding, or mucosal inflammation.
Therefore, Arthrotec should be used cautiously in these patients, starting treatment with the lowest effective dose.
Arthrotec should not be used in premenopausal women unless they are using effective contraception and have been informed of the risks associated with use during pregnancy. The packaging carries the warning: “Do not use in women of childbearing potential unless they are using effective contraception.”
Use of medicines such as Arthrotec 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. Do not exceed the recommended dose or duration of treatment.
Severe skin reactions have been very rarely observed during treatment with NSAIDs, including the combination drug containing diclofenac and misoprostol. The patient should immediately report any skin changes to the treating physician. The doctor may decide to discontinue treatment with Arthrotec at the first sign of skin rash, mucosal lesions, or any other hypersensitivity symptoms.
In patients with systemic lupus erythematosus or connective tissue diseases, Arthrotec may increase the risk of aseptic meningitis.
During long-term treatment with high doses of analgesic and/or anti-inflammatory drugs, headache may occur, which should not be treated by administering additional doses of the drug or other NSAIDs.
Arthrotec may mask fever and thus the underlying disease.
The drug may impair fertility. If a patient plans to become pregnant or has difficulty conceiving, she should inform her doctor.
Arthrotec may cause visual disturbances. If visual disturbances occur, consult an ophthalmologist.
Before taking the medicine, inform the doctor:

if the patient smokes
if the patient has diabetes
if the patient has angina pectoris, thrombosis, hypertension, elevated cholesterol, or elevated triglycerides.

The risk of adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary.
Arthrotec and other medicines
Inform the doctor if the patient is taking any of the following medicines:

diuretics (water tablets): NSAIDs may reduce the effectiveness of diuretics. When potassium-sparing diuretics are used concomitantly, serum potassium levels may increase; Page 3 of 9
cyclosporine (immunosuppressive drugs used, among others, in transplant patients): diclofenac may increase the nephrotoxicity of cyclosporine; it is important that in patients taking cyclosporine, treatment with Arthrotec begins with the lowest dose and the patient is carefully monitored for signs of toxic effects;
tacrolimus (an immunosuppressant used, among others, in atopic dermatitis): concomitant use of NSAIDs with tacrolimus may increase the risk of nephrotoxic effects;
lithium, digoxin, ketoconazole: Arthrotec may increase steady-state serum concentrations of lithium and digoxin, and decrease ketoconazole levels;
antidiabetic medicines: NSAIDs may enhance the effect of oral antidiabetic drugs. Concomitant use may increase the risk of hypoglycemia or hyperglycemia;
anticoagulants such as warfarin, antiplatelet agents such as acetylsalicylic acid. Concomitant use of Arthrotec with acetylsalicylic acid is not recommended;
selective serotonin reuptake inhibitors (SSRIs) (some antidepressants): NSAIDs may potentiate the effects of these drugs, thereby increasing the risk of gastrointestinal bleeding;
methotrexate: NSAIDs may enhance methotrexate toxicity due to increased plasma concentrations, especially in patients receiving high doses of methotrexate;
other NSAIDs and corticosteroids: concomitant use with Arthrotec may increase the frequency of gastrointestinal ulcers or bleeding and other adverse effects;
antihypertensive medicines, including diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (AIIA), and ß-blockers: NSAIDs may reduce their effectiveness. In patients with impaired renal function (e.g. dehydrated patients or elderly patients with renal impairment), concomitant administration of an ACE inhibitor or AIIA and/or diuretics with a cyclooxygenase inhibitor may lead to renal dysfunction, including acute renal failure, which is usually reversible;
antacids: these may delay absorption of diclofenac. Antacids containing magnesium may worsen diarrhea caused by misoprostol;
quinolones: patients taking NSAIDs and quinolones may have an increased risk of seizures;
mifepristone (an abortion drug not available in Poland): NSAIDs may reduce its efficacy. NSAIDs should be used at least 8 to 12 days after mifepristone administration;
voriconazole (an antifungal medicine);
sulfinpyrazone (a medicine used in the treatment of gout).

Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines you plan to take.
Arthrotec with food and drink
Tablets should be taken with food.
Pregnancy, breastfeeding, and fertility
Pregnancy
The patient should not take Arthrotec if she is pregnant, suspects she may be pregnant, or is trying to become pregnant. The patient should inform her doctor about a planned pregnancy. Due to the potential risk to the fetus, the patient must confirm she is not pregnant before starting treatment. Women of childbearing potential must use an effective method of contraception during treatment.
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The doctor must inform the patient about the risks associated with becoming pregnant while taking Arthrotec, as this medicine may cause miscarriage, premature birth, or fetal malformations (congenital abnormalities). If a patient is pregnant, she should NEVER take this medicine, as it may seriously harm the child, particularly affecting the heart, lungs, and/or kidneys, up to causing death. If a patient has taken this medicine during pregnancy, she should discuss it with her doctor. If the patient decides to continue the pregnancy, careful monitoring with ultrasound, particularly assessing fetal limbs and head, is required.
Diclofenac may cause premature closure of the ductus arteriosus.
NSAIDs used during the second or third trimester of pregnancy may cause renal dysfunction in the fetus, leading to oligohydramnios or, in severe cases, anhydramnios. These effects may appear soon after starting treatment and are usually reversible. Amniotic fluid volume should be closely monitored in pregnant women taking NSAIDs.
Breastfeeding
If the patient is breastfeeding, she should consult a doctor or pharmacist before taking this medicine. Do not use Arthrotec during breastfeeding. Misoprostol is metabolized to misoprostolic acid, which is excreted into breast milk and may cause adverse effects in breastfed infants, such as diarrhea.
Driving and operating machinery
Patients experiencing dizziness or other central nervous system disturbances while taking NSAIDs should not drive or operate machinery.
Arthrotec contains lactose monohydrate
If the patient has previously been diagnosed with intolerance to certain sugars, they should consult their doctor before taking this medicine.
Arthrotec contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is considered "sodium-free".
Arthrotec contains hydrogenated castor oil
The medicine contains hydrogenated castor oil, which may cause indigestion and diarrhea.

3. How to use Arthrotec

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
The tablets should be swallowed whole, not chewed.
Adults
The recommended dose is one tablet taken with food once to three times daily.
Use in elderly patients
Dose adjustment is not necessary; however, elderly patients should be closely monitored.
Use in patients with renal function impairment
Dose adjustment is not required in patients with mild or moderate renal function impairment, but they should be closely monitored.
Use in patients with hepatic function impairment
Dose adjustment is not required in patients with mild or moderate hepatic function impairment, but these patients should be closely monitored.
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Use in children and adolescents
Safety and efficacy have not been established in children and adolescents under 18 years of age.
Overdose of Arthrotec
In case of an overdose, contact your doctor or pharmacist immediately.
Treatment of acute poisoning with NSAIDs consists of supportive and symptomatic therapy. Measures aimed at reducing absorption of the recently ingested drug are recommended, such as inducing vomiting, gastric lavage, or administration of activated charcoal.
Clinical symptoms that may indicate mizoprostol overdose include: sedation, tremor, seizures, dyspnea, abdominal pain, diarrhea, fever, palpitations, hypotension, or bradycardia (slow heart rate). Inducing diuresis (urine excretion) may be beneficial, as metabolites of Arthrotec are excreted in urine.
Missed dose of Arthrotec
Do not take a double dose to make up for a missed dose.
Discontinuation of Arthrotec
The decision to discontinue treatment should be made by the doctor. If you feel the effect of the medicine is too strong or too weak, consult your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.

Very common (occurring in more than 1 in 10 patients):

abdominal pain, diarrhoea, nausea, dyspepsia

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

insomnia
headache, dizziness
gastrointestinal ulceration*, duodenitis, gastritis, oesophagitis, gastrointestinal inflammation*, vomiting, constipation, flatulence, regurgitation
rash*, pruritus
increased alanine aminotransferase activity, decreased haematocrit value, increased alkaline phosphatase activity in blood
fetal developmental abnormalities*

Uncommon (occurring in more than 1 in 1,000 and less than 1 in 100 patients):

vaginal inflammation
thrombocytopenia* (low platelet count)
stroke*
blurred vision*
myocardial infarction*, heart failure*
hypertension*
dyspnoea*
gastrointestinal haemorrhage*, stomatitis*
urticaria*, purpura

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irregular or intermenstrual menstrual bleeding, excessive menstrual bleeding, vaginal haemorrhage (including postmenopausal bleeding), menstrual disorders
fever*, oedema*, chills*
increased aspartate aminotransferase activity

Rare (occurring in less than 1 in 1,000 patients):

anaphylactic reaction*
nightmares*
pancreatitis*
hepatitis*
bullous dermatitis*, angioedema*
breast pain, dysmenorrhoea

Frequency unknown (cannot be estimated from the available data):

haemolytic anaemia*, agranulocytosis*, inhibition of platelet aggregation*
fluid retention*
mood changes*
aseptic meningitis* (characterised by symptoms such as neck stiffness, headache, nausea, vomiting, fever, or altered consciousness)
vasculitis*
gastrointestinal perforations*
liver failure*, jaundice*
toxic epidermal necrolysis*, Stevens-Johnson syndrome* (blisters of the oral and genital mucosa), erythema multiforme*, exfoliative dermatitis*, mucocutaneous reactions*, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)
renal failure*, renal function disorders*, renal papillary necrosis*, nephrotic syndrome*, interstitial nephritis*, membranous glomerulonephritis*, submicroscopic glomerulonephritis*, glomerulonephritis*
fetal death*, amniotic fluid embolism*, incomplete abortion*, premature delivery*, abnormal uterine contractions*, retained placenta or fetal membranes*
uterine haemorrhage*, uterine contractions, female infertility (reduced fertility in women)*
uterine rupture*, uterine perforation*

* Adverse reactions reported after marketing authorization of the medicinal product.
Inform your doctor immediately if the patient experiences chest pain, which may be a symptom of a potentially severe allergic reaction called Kounis syndrome.
Adverse reactions from controlled clinical trials lasting up to 24 months are mainly related to the gastrointestinal system. Diarrhoea and abdominal pain are usually mild or moderate in severity and transient; these symptoms occur early in treatment and may last for several days. Diarrhoea and abdominal pain resolve spontaneously during treatment with Arthrotec.
When using NSAIDs, exacerbation of inflammation associated with infection has been observed in very rare cases.
After marketing authorization, the most commonly reported adverse reactions were gastrointestinal disorders (approximately 45% of all reported cases), followed by skin and hypersensitivity reactions, which is consistent with the adverse reaction profile of NSAIDs.
The use of diclofenac, particularly at high doses (150 mg daily) and during long-term treatment, may be associated with a slightly increased risk of serious arterial thrombotic events (e.g. myocardial infarction or stroke).
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Reporting of adverse reactions
If any adverse effects occur, including any possible adverse effects not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration 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
Reporting adverse reactions enables the collection of additional information on the safety of the medicine.

5. How to store Arthrotec

Keep this medicine out of the 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 stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Arthrotec contains

The active substances are diclofenac and misoprostol. Each tablet consists of a gastro-resistant core containing 50 mg of diclofenac sodium, coated with an outer layer containing 0.2 mg of misoprostol.

The other ingredients are: monohydrate lactose, microcrystalline cellulose, maize starch,
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 with "A" on one side and "SEARLE 1411"
on the other side.
Pack contents: 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, please contact the responsible party or parallel importer.
Responsible party in Portugal, country of export:
Laboratórios Pfizer, Lda., Lagoas Park, Edifício 10, 2740-271 Porto Salvo, Portugal
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Manufacturer:
Piramal Pharma Solutions (Dutch) B.V., Level, 7th floor, Bargelaan 200, 2333 CW, Leiden,
Netherlands
Parallel importer:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Repackaged in:
Delfarma Sp. z o.o., ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Portugal, country of export, marketing authorization number: 8786210
Parallel import authorization number: 408/22
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