Refastin

Package leaflet: Information for the patient

Refastin, 100 mg, film-coated tablets
Ketoprofen
Please read the entire leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. The medicine may harm someone else, even if their symptoms are similar.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

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

1. What Refastin is and what it is used for

Refastin contains ketoprofen, which belongs to the group of non-steroidal anti-inflammatory drugs with analgesic and antipyretic properties. Its mechanism of action involves inhibition of prostaglandin synthesis.
Indications

• Symptomatic treatment of:
  • rheumatic diseases, including rheumatoid arthritis and osteoarthritis;
  • degenerative joint disorders associated with mild to moderate pain and significantly impaired patient mobility.
• Mild to moderate pain of various origins.
• Painful menstruation.

2. Important information before using Refastin

When not to use Refastin:

• if the patient has previously experienced hypersensitivity reactions such as bronchospasm, asthma attack, rhinitis, angioedema, urticaria, or other types of allergic reactions after taking ketoprofen, acetylsalicylic acid, or other non-steroidal anti-inflammatory drugs (NSAIDs), because severe, rarely fatal anaphylactic reactions have been reported in such patients;
• if the patient is allergic to ketoprofen or any of the other ingredients of this medicine (listed in section 6);
• if the patient has active gastric or duodenal ulcer, or has previously experienced gastrointestinal bleeding, ulcers, or gastrointestinal perforation;
• if the patient has severe hepatic impairment;
• if the patient has severe renal impairment;
• if the patient is in the third trimester of pregnancy;
• if the patient has severe heart failure;
• if the patient has a bleeding tendency.

Warnings and precautions
Before starting treatment with Refastin, discuss this with your doctor or pharmacist.
Inform your pharmacist or doctor if the patient has an infection – see below, section titled "Infections".
It is very important to take Refastin at the lowest effective dose for the shortest duration necessary to relieve symptoms – this minimizes the risk of gastrointestinal and cardiovascular adverse effects.
Avoid concomitant use of ketoprofen with other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors and high-dose salicylates, due to the possibility of increased adverse effects.
Patients with bronchial asthma, chronic rhinitis, chronic sinusitis, or nasal polyps may experience asthma attacks or bronchospasm, particularly those hypersensitive to acetylsalicylic acid or other NSAIDs.
Use of ketoprofen (especially at high doses) may carry a high risk of adverse effects on the gastrointestinal tract. With long-term NSAID therapy, there is a risk of gastrointestinal bleeding, gastric or duodenal ulceration, and perforation, which may be fatal, even in the absence of warning symptoms, particularly in patients with a history of gastrointestinal ulcers and in elderly patients.
Exercise caution when using NSAIDs in patients with a history of gastrointestinal disorders (e.g. gastritis, duodenitis, ulcerative colitis, Crohn's disease), due to the possibility of symptom exacerbation.
If any gastrointestinal disturbances occur, especially gastrointestinal bleeding, discontinue the medicine and consult a doctor. The doctor will exercise caution when prescribing ketoprofen to patients with a history of stomach or intestinal disorders.
In case of mild gastrointestinal adverse effects, gastroprotective agents (e.g. misoprostol) may be used.
Exercise caution in patients taking medications that may increase the risk of gastrointestinal ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g. warfarin), selective serotonin reuptake inhibitors (SSRIs), or antiplatelet agents such as acetylsalicylic acid (see section "Refastin with other medicines" below).

Infections
Refastin may mask objective signs of infection such as fever and pain. Therefore, Refastin may delay appropriate treatment of infection and consequently increase the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections associated with varicella. If the patient is taking this medicine during an ongoing infection and symptoms persist or worsen, consult a doctor immediately.

Patients with a history of photosensitivity reactions or phototoxicity should be closely monitored by a physician during ketoprofen treatment.

Very rarely, severe skin reactions (including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis) have been reported with NSAID use, especially at the beginning of treatment. If early signs suggestive of severe skin reactions or hypersensitivity occur—such as skin rash, oral mucosal lesions, or other hypersensitivity symptoms—discontinue the medicine and contact a doctor immediately.

Exercise caution in patients with systemic lupus erythematosus or mixed connective tissue disease due to an increased risk of aseptic meningitis.

NSAIDs may have a toxic effect on the kidneys, potentially leading to interstitial nephritis, nephrotic syndrome, and renal failure.

In elderly patients, and in those with heart failure, hepatic dysfunction, liver cirrhosis, nephrotic syndrome, chronic renal impairment, or fluid imbalance (e.g. dehydration due to diuretic use or other causes), ketoprofen may impair renal function, leading to edema and increased serum nitrogen levels.

In patients with hypertension and/or heart failure, particularly in the elderly, fluid and sodium retention and edema may occur.

Particular caution is advised when using ketoprofen in elderly patients, especially those with hepatic or renal impairment. During long-term ketoprofen therapy, the doctor may recommend regular monitoring of blood morphology, liver function, and kidney function tests, and may adjust the dose individually according to the patient's condition.

If visual disturbances such as blurred vision occur, discontinue the medicine.

Use of medicines such as Refastin may be associated with a small increased risk of myocardial infarction (heart attack) or stroke. This risk increases with prolonged use of high doses. Do not exceed the recommended dose or duration of treatment. If the patient has heart problems, a history of stroke, cerebrovascular disease, peripheral arterial disease, or risk factors for these conditions (e.g. high blood pressure, diabetes, elevated cholesterol, smoking), discuss treatment options with a doctor.

Children and adolescents
The safety of ketoprofen use in children and adolescents has not been established.
Do not use in patients under 15 years of age.

Refastin with other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines planned for future use.

Concomitant use of ketoprofen with the following medicines is not recommended:

• other analgesics and/or anti-inflammatory drugs (including COX-2 inhibitors), high-dose salicylates;
• anticoagulants (drugs that inhibit blood coagulation) such as warfarin, acenocoumarol, and parenteral heparin;
• antiplatelet agents (drugs that inhibit platelet aggregation) such as clopidogrel or ticlopidine;
• lithium (a medicine used in the treatment of psychiatric disorders);
• methotrexate (a medicine used in oncological and rheumatological conditions) at doses exceeding 15 mg per week.

Exercise caution and consult a doctor before using ketoprofen if the patient is taking:

• diuretics;
• methotrexate (at doses less than 15 mg per week);
• pentoxifylline (a medicine used in circulatory disorders);
• quinolone antibiotics;
• antihypertensive medicines (β-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists);
• thrombolytic agents (used to clear blood vessels);
• selective serotonin reuptake inhibitors (SSRIs) (medicines used, among others, to treat depression);
• probenecid (a medicine used, among others, in the treatment of gout);
• cyclosporine (a medicine used to prevent rejection of transplanted organs or bone marrow);
• tacrolimus (an immunosuppressive medicine);
• corticosteroids (anti-inflammatory medicines);
• cardiac glycosides (e.g. digoxin);
• mifepristone (a medicine used in gynecology);
• zidovudine (a medicine used in HIV-infected patients);
• hormonal contraceptives – ketoprofen may reduce their effectiveness;
• oral antidiabetic medicines, such as glimepiride.

Concomitant use of ketoprofen with antiplatelet agents (such as acetylsalicylic acid and other NSAIDs, ticlopidine, clopidogrel) and SSRIs increases the risk of bleeding, as does concomitant use of anticoagulants (including heparin and warfarin) and thrombolytic agents.
In patients receiving combination therapy, drug levels should be monitored and recommended tests performed regularly.

Refastin with food, drink, and alcohol
Take the medicine during a meal, with a glass of water.
The medicine may intensify the effects of alcohol.

Pregnancy, breastfeeding, and fertility
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor or pharmacist before using this medicine.

Pregnancy
Do not use Refastin if the patient is in the last three months of pregnancy, as it may harm the unborn child or cause problems during delivery. Refastin may cause kidney and heart problems in the unborn child. It may affect bleeding tendency in both the mother and the child and may delay or prolong labor.
Do not take Refastin during the first six months of pregnancy unless the doctor considers its use absolutely necessary. If treatment is needed during this period or when trying to conceive, use the lowest effective dose for the shortest possible time. From the 20th week of pregnancy, Refastin may cause impaired kidney function in the unborn child if used for longer than a few days. This may lead to low levels of amniotic fluid surrounding the baby (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the baby's heart. If treatment for longer than a few days is required, the doctor may recommend additional monitoring.

Breastfeeding
Use of this medicine is not recommended during breastfeeding.

Effect on fertility
Ketoprofen use may adversely affect fertility in women and is not recommended for women planning to become pregnant. In women experiencing difficulty conceiving or undergoing fertility investigations, discontinuation of ketoprofen should be considered.

Driving and operating machinery
If drowsiness, dizziness, seizures, fatigue, or visual disturbances occur during ketoprofen treatment, do not drive or operate machinery.

Refastin contains lactose and quinoline yellow (E 104)
If the patient has previously been diagnosed with intolerance to certain sugars, consult a doctor before taking this medicine.
The medicine may cause allergic reactions.

3. How to use Refastin

This medicine should always be used according to the doctor's instructions. In case of doubt, consult
your doctor or pharmacist.
The medicine is taken orally. Tablets should be taken during a meal, with a glass of water.
The tablet should be swallowed whole, without chewing.
The lowest effective dose for the shortest necessary duration should be used to relieve symptoms
and reduce the risk of adverse effects. If symptoms of infection (such as fever and pain) persist or
worsen during treatment, medical advice should be sought immediately (see section 2).

Recommended dose
Adults
For long-term symptomatic treatment: 1 or 2 tablets per day, i.e. 100 mg or 200 mg per day,
in one or two divided doses.
For short-term symptomatic treatment of acute conditions: 3 tablets per day, i.e. 300 mg per day,
in three divided doses.

Children and adolescents
The safety of ketoprofen use in children and adolescents has not been established.
Do not use in patients under 15 years of age.

Use of a higher than recommended dose of Refastin
If a higher than recommended dose is taken, seek immediate advice from a doctor or pharmacist.
Symptoms observed after ketoprofen overdose include: lethargy, headache, drowsiness, nausea,
vomiting, diarrhoea, abdominal pain, disorientation, agitation, coma, dizziness, tinnitus,
fainting, convulsions, hypotension, breathing difficulties, gastrointestinal bleeding.
In cases of overdose with high doses of ketoprofen, acute renal failure and liver damage may occur.
In case of overdose, discontinue the medicine immediately and contact a doctor.
Appropriate management will be initiated by medical personnel.

Missed dose of Refastin
Do not take a double dose to make up for a missed dose.
Resume the dosing regimen as prescribed by the doctor.
If you have any further doubts regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everybody will experience them.
The most commonly observed adverse effects involve the gastrointestinal system. Particularly in elderly patients, gastric ulcers, gastrointestinal perforation or gastrointestinal bleeding may occur, sometimes with fatal outcome.

Adverse effects are listed below by frequency:

Common (may affect up to 1 in 10 people):

• Dyspepsia, nausea, abdominal pain, vomiting.

Uncommon (may affect up to 1 in 100 people):

• Headache, dizziness, constipation, diarrhoea, flatulence, gastritis, skin rash, pruritus, fatigue, oedema.

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

• Blood count abnormalities (haemorrhagic anaemia, bleeding-induced anaemia, leukopenia with possible agranulocytosis), anaphylactic reactions (including anaphylactic shock), paresthesia (tingling, burning, stinging sensations in limbs), visual disturbances such as blurred vision, tinnitus, bronchial asthma, asthmatic attacks, stomatitis, peptic ulcer of the stomach and/or duodenum, hepatitis, increased aminotransferase activity, increased serum bilirubin associated with hepatitis, weight gain.

Very rare (may affect up to 1 in 10,000 people):

• Pancreatitis.

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

• Blood count abnormalities (agranulocytosis, thrombocytopenia, neutropenia), bone marrow suppression, mood disturbances, convulsions, taste disturbances, depression, confusion, hallucinations, vertigo, malaise, optic neuritis, cardiac failure, vasodilation, hypertension, bronchospasm (especially in patients with diagnosed hypersensitivity to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs), rhinitis, dyspnoea, non-specific allergic reactions, exacerbation of colitis and Crohn's disease, gastrointestinal bleeding and perforation (sometimes with fatal outcome, especially in elderly patients), abdominal pain, melena, haematemesis, hepatic function disorders, jaundice, photophobia, erythema, alopecia, urticaria, bullous skin eruptions including Stevens-Johnson syndrome and Lyell's syndrome, toxic epidermal necrolysis, erythema multiforme, purpura, angioedema, acute renal failure (especially in patients with pre-existing renal impairment and/or dehydrated patients), interstitial nephritis, nephrotic syndrome, abnormal renal function test results, disturbances in taste perception. Cases of aseptic meningitis (particularly in patients with systemic lupus erythematosus or mixed connective tissue disease) with symptoms such as neck stiffness, headache, nausea, vomiting, fever or feeling disoriented.

Clinical studies and epidemiological data indicate that use of certain NSAIDs (particularly long-term and at high doses) is associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).

If any serious adverse effects occur, treatment with Refastin should be discontinued immediately.

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Refastin

Keep this medicine out of sight and reach of children.
Do not store above 25°C. Protect from light and 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.
The marking on the packaging following the abbreviation EXP indicates the expiry date, and the abbreviation Lot/LOT indicates the batch number.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Refastin contains

• The active substance is ketoprofen. Each coated tablet contains 100 mg of ketoprofen.
• The other ingredients are:
• tablet core – microcrystalline cellulose, crospovidone, colloidal anhydrous silica, magnesium stearate.
• tablet coating – hypromellose, lactose monohydrate, triacetin, titanium dioxide (E 171), macrogol 3000, quinoline yellow (E 104), iron oxide yellow (E 172), iron oxide red (E 172).

What Refastin looks like and contents of the pack
20 tablets or 30 tablets in aluminium/PVDC blisters, packed in a cardboard box.
Marketing Authorisation Holder
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01
Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
Medana Branch in Sieradz
ul. Władysława Łokietka 10, 98-200 Sieradz
Zakłady Farmaceutyczne POLPHARMA S.A.
Production Branch in Nowa Dęba
ul. Metalowca 2
39-460 Nowa Dęba