Febrofen

Package leaflet: information for the patient

Febrofen, 200 mg, prolonged-release capsules
Ketoprofenum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What Febrofen is and what it is used for

Febrofen contains ketoprofen, which belongs to a group of non-steroidal anti-inflammatory drugs with analgesic and antipyretic properties.
Febrofen is a formulation characterized by controlled release of the active substance over time; the release of the active substance occurs in the alkaline environment of the small intestine. Ketoprofen is highly bound to plasma proteins, mainly albumins. It is metabolized in the liver and excreted, mainly in the form of inactive metabolites, 80% via urine.
Indications
Symptomatic treatment of chronic inflammatory rheumatic diseases, especially rheumatoid arthritis.
Symptomatic treatment of severe degenerative joint changes, when the required daily dose is 200 mg.

2. Important information before using Febrofen

When not to use Febrofen

• if the patient has previously experienced hypersensitivity reactions such as bronchospasm, bronchial asthma attack, rhinitis, angioedema, urticaria, or other types of allergic reactions after administration of 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 components of this medicine (listed in section 6);
• if the patient has active gastric or duodenal ulceration, or has previously experienced gastrointestinal bleeding, ulceration, or perforation;
• if the patient has severe hepatic or renal insufficiency;
• if the patient is in the third trimester of pregnancy;
• if the patient has severe heart failure;
• if the patient has a bleeding disorder.

Warnings and precautions
Before starting treatment with Febrofen, 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 Febrofen 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 potential for increased adverse effects.
In patients with bronchial asthma, chronic rhinitis, chronic sinusitis, and/or nasal polyps, asthma attacks or bronchospasm may occur (particularly in individuals hypersensitive to acetylsalicylic acid or other NSAIDs).
Use of ketoprofen (especially at high doses) may be associated with a high risk of harmful effects on the gastrointestinal tract. With long-term NSAID therapy, there is a risk of gastrointestinal bleeding, 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), as symptoms may worsen.
If any gastrointestinal disturbances occur, especially gastrointestinal bleeding, discontinue the drug and consult a doctor. Physicians should exercise caution when prescribing ketoprofen to patients with a history of gastric or intestinal disorders.
In case of mild gastrointestinal adverse effects, mucosal protective 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 below “Febrofen with other medicines”).

Infections
Febrofen may mask signs of infection such as fever and pain. Therefore, Febrofen 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 chickenpox. If the patient is taking this medicine during an ongoing infection and symptoms of infection persist or worsen, contact a doctor immediately.

Patients with a history of photosensitivity reactions or phototoxicity will 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 the use of NSAIDs, particularly at the beginning of treatment. If the first signs suggestive of severe skin reactions or hypersensitivity occur—such as skin rash, oral mucosal lesions, or other hypersensitivity symptoms—discontinue the drug 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, as well as in those with heart failure, hepatic dysfunction, liver cirrhosis, nephrotic syndrome, chronic renal impairment, or fluid imbalances (e.g., dehydration due to diuretic use or other causes), ketoprofen may impair renal function, potentially causing 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 impaired liver or kidney function. During long-term ketoprofen therapy, the physician may recommend regular blood morphology tests and monitoring of liver and kidney function, adjusting the ketoprofen dose individually according to the patient's condition.

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

Use of medicines such as Febrofen 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 suspected risk of these conditions (e.g., high blood pressure, diabetes, high cholesterol, smoking), discuss the treatment approach with a doctor.

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

Febrofen 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/anti-inflammatory drugs (including COX-2 inhibitors) and high-dose salicylates;
• anticoagulants (drugs that inhibit blood clotting) such as warfarin, acenocoumarol, and parenterally administered 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 your 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-adrenergic receptor 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, in the treatment of 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);
• potassium salts (used in the treatment of potassium deficiency);
• trimethoprim (a medicine used, among others, in urinary tract infections);
• oral antidiabetic medicines;
• corticosteroids (anti-inflammatory medicines);
• cardiac glycosides (e.g., digoxin);
• mifepristone (a medicine used in gynecology);
• oral contraceptives.

Concomitant use of antiplatelet drugs (such as acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, ticlopidine, clopidogrel) and selective serotonin reuptake inhibitors increases the risk of bleeding, similarly to concomitant administration of anticoagulant drugs (including heparin and warfarin) and thrombolytic agents.
In patients receiving combination therapy, drug levels should be monitored and recommended tests performed regularly.
Aluminium-containing antacids do not reduce ketoprofen absorption.
Febrofen with food, drink and alcohol
The medicine should be taken during a meal, with a glass of water.
The medicine may enhance the effects of alcohol.
Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult her doctor or pharmacist before taking this medicine.
Pregnancy
Febrofen should not be used during the last three months of pregnancy, as it may harm the unborn child or cause problems during delivery. Febrofen may cause kidney and heart problems in the unborn child. It may also affect the tendency to bleeding in both the mother and her child, and may delay or prolong labour.
Febrofen should not be taken during the first six months of pregnancy unless the doctor considers its use absolutely necessary. If treatment is required during this period or when trying to become pregnant, the lowest effective dose for the shortest possible duration should be used. From the 20th week of pregnancy, Febrofen may cause kidney function disturbances in the unborn child if taken 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 the medicine during breastfeeding is not recommended.
Fertility
Ketoprofen use may adversely affect female fertility and is not recommended in women attempting to conceive. In women experiencing difficulty becoming pregnant or undergoing infertility investigations, discontinuation of ketoprofen should be considered.
Driving and operating machinery
If drowsiness, dizziness, seizures, fatigue or visual disturbances occur during treatment with ketoprofen, driving and operating machinery should be avoided.
Febrofen contains sucrose
If the patient has been previously diagnosed with intolerance to certain sugars, the patient should consult their doctor before taking this medicine.

3. How to use Febrofen

This medicine should always be taken exactly as directed by the doctor. If in doubt, consult
your doctor or pharmacist.
The medicine is taken orally. The capsules should be taken during a meal. The capsule should be swallowed
whole with a glass of water.
To minimize the risk of adverse effects, use the lowest effective dose for the shortest duration necessary
to relieve symptoms. If symptoms of an infection (such as fever and pain) persist or worsen,
you should contact your doctor immediately (see section 2).

Recommended dose
Adults
One 200 mg capsule once daily.
In case of mild gastrointestinal disturbances, it may be beneficial to use drugs that neutralize or protect
the gastric mucosa. Aluminum-containing compounds with neutralizing action do not reduce
ketoprofen absorption.
The maximum daily dose of ketoprofen is 200 mg (one capsule).

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

Taking more Febrofen than recommended
If you take more medicine than recommended, contact your doctor or pharmacist immediately.
Symptoms observed after ketoprofen overdose include: lethargy, headache, drowsiness, nausea,
vomiting, diarrhoea, abdominal pain, disorientation, agitation, coma, dizziness, tinnitus,
fainting, convulsions, hypotension, breathing difficulties, and gastrointestinal bleeding.
After large overdoses of ketoprofen, acute renal failure and liver damage may occur.
In case of overdose, discontinue the medicine immediately and contact your doctor.
Appropriate management will be provided by medical personnel.

Missing a dose of Febrofen
Do not take a double dose to make up for a missed dose.
Resume the dosing schedule as prescribed by your doctor.
If you have any further doubts about 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 everyone will experience them.
The most commonly observed adverse effects are gastrointestinal. Particularly in elderly patients, gastric ulcers, perforation or gastrointestinal bleeding may occur, sometimes with fatal outcome. Oral ketoprofen at a daily dose of 200 mg increases the risk of gastrointestinal bleeding, and the risk increases with increasing dose.
Adverse effects are listed below according to their frequency of occurrence:

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, somnolence, constipation, diarrhoea, flatulence, gastritis, rash, pruritus, fatigue, oedema.

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

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

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

• pancreatitis.

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

• blood count abnormalities (agranulocytosis, thrombocytopenia, neutropenia), bone marrow suppression, mood disturbances, depression, confusion, hallucinations, optic neuritis, convulsions, taste disturbances, vestibular dizziness, heart failure, vasodilation, hypertension, bronchospasm (particularly in patients diagnosed with hypersensitivity to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs), 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, heartburn, melaena, haematemesis, liver function disorders, jaundice, erythema, photosensitivity, alopecia, urticaria,
  bullous skin eruptions, including Stevens-Johnson syndrome and Lyell's syndrome, exfoliative and bullous skin disorders (including toxic epidermal necrolysis, erythema multiforme), purpura, angioedema, acute renal failure (particularly in patients with pre-existing renal impairment and/or dehydrated patients), interstitial nephritis, nephrotic syndrome, abnormal kidney function test results, malaise, rhinitis, hyperkalemia.
  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 disorientation.

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

In the event of any serious adverse effects, administration of Febrofen must be discontinued immediately.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring 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 to provide more information on the safety of this medicine.

5. How to store Febrofen

Store below 25ºC. Protect from light and moisture.
Keep the medicine in a place out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton. The expiry date refers to the last day of the stated month.
The packaging label shows EXP followed by the expiry date, and Lot/LOT followed by the batch number.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This helps protect the environment.

6. Contents of the package and other information

What Febrofen contains

• The active substance is ketoprofen. Each capsule contains 200 mg of ketoprofen.
• The other ingredients are: macrogol 4000, ethylcellulose, stearic acid, ammonio methacrylate copolymer (type B) – Eudragit RS, shellac, talc, red iron oxide (E 127), titanium dioxide (E 171), gelatin.

What Febrofen looks like and contents of the pack
Febrofen is a hard gelatin capsule with a transparent cap and a pink cap, containing white or almost white spherical microgranules.
The medicine is available in aluminium/PVC blisters in cardboard packaging containing 20, 30, 60 or 90 capsules.

Marketing Authorisation Holder
Zakłady Farmaceutyczne POLPHARMA S.A.
Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01

Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
Medana Branch in Sieradz
Władysława Łokietka 10, 98-200 Sieradz

Zakłady Farmaceutyczne POLPHARMA S.A.
Production Unit in Nowa Dęba
Metalowca 2, 39-460 Nowa Dęba