Metafen

Package leaflet: Information for the patient

Metafen, 200 mg + 325 mg, coated tablets
Ibuprofenum + Paracetamolum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.
This medicine should always be used exactly as described in this patient leaflet or as directed by a
physician or pharmacist.

• Keep this leaflet so that you can read it again if necessary.
• If you need advice or further information, please consult your pharmacist.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.
• If there is no improvement after 3 days, or if you feel worse, consult your doctor.

Table of contents

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

1. What Metafen is and what it is used for

Metafen is a medicine in the form of coated tablets for oral administration.
It contains two active substances – ibuprofen and paracetamol – which have analgesic, antipyretic, and anti-inflammatory properties.
Indications for use:

• Pain of various origins, including:
  • headaches
  • migraine
  • menstrual pain
  • toothache
  • muscle pain
  • bone and joint pain
  • lumbosacral pain
  • post-traumatic pain
  • neuralgia
• fever.

This medicine is intended for adults and adolescents over 12 years of age.

2. Important information before using Metafen

When not to use Metafen:

• if the patient is allergic to paracetamol, ibuprofen, or any of the other ingredients of this medicine (listed in section 6);
• if the patient has hypersensitivity to drugs from the NSAID group (non-steroidal anti-inflammatory drugs), including acetylsalicylic acid; if in the past there was aspirin-induced asthma, angioedema (a skin and mucous membrane disorder characterized by swelling), bronchospasm, rhinitis, or urticaria associated with taking acetylsalicylic acid or other NSAIDs;
• if the patient has severe renal and/or hepatic insufficiency;
• if the patient has or has had peptic ulcer disease of the stomach and/or duodenum, perforations, or gastrointestinal bleeding, including those occurring after using NSAIDs;
• if the patient has severe hypertension;
• if the patient has severe cardiovascular diseases, tachycardia (rapid heartbeat), or angina pectoris;
• if the patient has severe heart failure;
• if the patient has a bleeding tendency (haemorrhagic diathesis);
• if the patient is taking other non-steroidal anti-inflammatory drugs, including COX-2 inhibitors, and acetylsalicylic acid at a daily dose exceeding 75 mg;
• if the patient is taking other medicines containing paracetamol;
• during pregnancy and breastfeeding;
• in children under 12 years of age.

Warnings and precautions
Before starting treatment with Metafen, discuss it with your doctor or pharmacist.
Metafen contains paracetamol. To avoid overdose, check whether other medicines the patient is taking also contain paracetamol (see section 2).
Prolonged, simultaneous use of various analgesic drugs may lead to kidney damage with risk of renal failure. There is a risk of impaired kidney function in dehydrated adolescents.
Exercise caution when using this medicine in patients:

• with impaired liver and/or kidney or cardiovascular function; in patients with kidney dysfunction, use the smallest effective doses;
• with bronchial asthma or those who have or have had other allergic reactions, due to the risk of bronchospasm;
• with systemic lupus erythematosus or mixed connective tissue disease – increased risk of developing aseptic meningitis;
• with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease) – symptoms may worsen; particularly caution is required in patients over 65 years of age, as especially with long-term use there is a risk of gastrointestinal bleeding, ulcers, or perforation. If any unusual gastrointestinal symptoms occur, especially in the initial treatment period, discontinue the medicine immediately and consult a doctor.
• with cardiac arrhythmias, hypertension, myocardial infarction, or heart failure – fluid retention may occur due to worsening kidney function;
• with coagulation disorders who are simultaneously taking other drugs that may increase the risk of gastrointestinal disorders or increase the risk of bleeding, such as corticosteroids or anticoagulants like warfarin (acenocoumarol), certain antidepressants (see "Metafen with other medicines"), or antiplatelet drugs like acetylsalicylic acid;
• with heart function disorders, history of stroke, or suspected risk of such disorders (e.g. high blood pressure, diabetes, elevated cholesterol, smoking) – discuss treatment approach with your doctor or pharmacist; patients over 65 years of age have a higher risk of adverse effects than younger patients; if the patient has an infection – see below, section titled "Infections".

Infections
Metafen may mask symptoms of infection such as fever and pain. Therefore, Metafen 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 takes this medicine during an existing infection and infection symptoms persist or worsen, consult a doctor immediately.

Skin reactions
Severe skin reactions associated with the use of Metafen have been reported. If any skin rash, mucosal changes, blisters, or other allergic symptoms appear, discontinue taking Metafen immediately and seek medical help promptly, as these may be early signs of a very serious skin reaction. See section 4.

This medicine belongs to a group of drugs (non-steroidal anti-inflammatory drugs, NSAIDs) which may adversely affect fertility in women. This effect is reversible and resolves after discontinuation of treatment. Ibuprofen may impair fertility. If a patient plans pregnancy or has difficulty conceiving, she should inform her doctor.

Taking the medicine at the lowest effective dose for the shortest duration necessary to relieve symptoms reduces the risk of adverse effects.

Use of this medicine may lead to false results in certain laboratory tests performed by redox methods (e.g. blood glucose measurement).

Taking anti-inflammatory/analgesic medicines such as ibuprofen may be associated with a small increased risk of heart attack or stroke, particularly when used at high doses. Do not exceed the recommended dose or duration of treatment.

Before using Metafen, the patient should discuss treatment with a doctor or pharmacist if:

• the patient has heart diseases such as heart failure, angina pectoris (chest pain), history of heart attack, coronary artery bypass surgery, peripheral artery disease (poor blood circulation in legs due to narrowed or blocked arteries), or history of stroke (including mini-stroke or transient ischemic attack - TIA).
• the patient has hypertension, diabetes, elevated cholesterol levels, family history of heart disease or stroke, or if the patient smokes.

During treatment with Metafen, inform the doctor immediately if the patient develops severe conditions, including severe kidney dysfunction or sepsis (when bacteria and their toxins circulate in the blood, leading to organ damage), malnutrition, chronic alcoholism, or if the patient is also taking flucloxacillin (an antibiotic). In such cases, patients have experienced a serious condition called metabolic acidosis (a blood and body fluid abnormality) when taking paracetamol regularly over a long period or when taking paracetamol together with flucloxacillin. Symptoms of metabolic acidosis may include: severe breathing difficulties, including rapid deep breathing, drowsiness, nausea, and vomiting.

Metafen with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

As with any other medicine containing paracetamol, avoid using Metafen together with other medicines containing paracetamol due to increased risk of serious adverse effects.

Metafen may affect other medicines, and some medicines may affect this medicine.

Do not take Metafen simultaneously with:

• acetylsalicylic acid (except for a low dose of 75 mg per day as prescribed by a doctor);
• other non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors, as these drugs increase the risk of adverse effects.

Metafen may be used with caution together with the following medicines. However, consult your doctor or pharmacist first if the patient is taking medicines such as:

• chloramphenicol (used for bacterial infections) – accelerates paracetamol absorption;
• cholestyramine (used to reduce cholesterol levels) – reduces the rate of paracetamol absorption;
• metoclopramide and other drugs enhancing peristalsis (movement of food and digestive products through the gastrointestinal tract) – accelerate paracetamol absorption;
• domperidone (anti-emetic medicine) – increases paracetamol absorption;
• anticoagulant medicines (i.e. blood thinners/preventing clot formation, such as aspirin/acetylsalicylic acid, warfarin, ticlopidine) – increased risk of bleeding during regular use of paracetamol;
• rifampicin (antibiotic), antiepileptic drugs, and barbiturates (used as anticonvulsants and sedatives) – risk of liver damage;
• antidepressants belonging to the monoamine oxidase inhibitors (MAO inhibitors) group – may cause agitation and high fever;
• selective serotonin reuptake inhibitors (SSRIs) – increased risk of gastrointestinal bleeding;
• propantheline and other drugs inhibiting peristalsis – delay paracetamol absorption;
• blood pressure-lowering medicines (ACE inhibitors such as captopril, beta-blockers such as atenolol-containing drugs, angiotensin II receptor antagonists such as losartan) – NSAIDs may reduce the effectiveness of these medicines;
• corticosteroids (anti-inflammatory medicines), antiplatelet medicines – increased risk of gastrointestinal bleeding;
• cardiac glycosides (used, e.g., in heart failure) – NSAIDs may worsen heart failure;
• cyclosporine (used after organ transplants) – increased risk of kidney toxicity;
• diuretics – may increase the risk of nephrotoxic effects of NSAIDs; additionally, NSAIDs may reduce the effectiveness of diuretics;
• methotrexate (used in cancer diseases) and lithium salts (used in psychiatry) – may lead to increased adverse effects due to elevated blood concentrations;
• mifepristone – NSAIDs reduce its effectiveness;
• quinolone antibiotics (e.g. ciprofloxacin) – used with NSAIDs may increase the risk of seizures;
• tacrolimus (used after transplants and in atopic dermatitis) – increased risk of nephrotoxicity;
• zidovudine (antiviral medicine) – increased risk of hematological toxicity;
• flucloxacillin (antibiotic) – due to serious risk of blood and body fluid disorders (called metabolic acidosis), which require urgent treatment (see section 2).

Other medicines may also influence or be influenced by treatment with Metafen. Therefore, always consult a doctor or pharmacist before using Metafen with other medicines.

Metafen with food, drink, and alcohol
Do not consume alcohol while taking Metafen, as there is a risk of toxic liver damage, especially in malnourished individuals and regular alcohol drinkers.
It is recommended to take Metafen after a meal (see section 3).

Pregnancy, breastfeeding, and effect on fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine.
Metafen is contraindicated throughout pregnancy and breastfeeding.
Do not use Metafen during pregnancy, as it may harm the unborn child or cause complications during delivery. It may cause kidney and heart dysfunction in the unborn child. It may increase the tendency to bleeding in the patient and her child and may delay or prolong labour.
Metafen taken for longer than a few days starting from the 20th week of pregnancy may cause kidney disorders in the unborn child, which 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.
Effect on fertility – see section "Warnings and precautions".

Driving and operating machinery
After taking the medicine, adverse effects such as dizziness, drowsiness, fatigue, and visual disturbances may occur. Patients experiencing these symptoms should not drive or operate machinery.

3. How to use Metafen

This medicine should always be taken exactly as described in this patient information leaflet or as directed by a doctor or pharmacist. If in doubt, consult your doctor or pharmacist.
For oral use.
It is recommended to take the medicine after a meal.

Recommended dose:
Adults: 1 or 2 coated tablets at a time.
If necessary, the dose may be repeated up to 3 times daily.
Do not take more than 6 coated tablets per day.

Elderly patients: Dose adjustment is not required. However, elderly patients have an increased risk of developing severe complications from adverse effects. If treatment is necessary, the lowest effective dose should be used for the shortest possible duration.

Children and adolescents
Adolescents over 12 years of age: 1 coated tablet at a time.
If necessary, the dose may be repeated up to 3 times daily.
Do not take more than 3 coated tablets per day.
Use the lowest effective dose for the shortest period necessary to relieve symptoms. If symptoms of infection persist or worsen (such as fever and pain), consult a doctor immediately (see section 2).

For short-term use only.
Patients should consult a doctor if symptoms persist or worsen, or if treatment longer than 3 days is required.

Overdose of Metafen
If an overdose is taken, symptoms of overdose may occur.
Early symptoms of overdose are related to the action of ibuprofen, while later symptoms are related to paracetamol.

If a patient has taken more than the recommended dose of Metafen, or if a child has accidentally taken the medicine, always consult a doctor or go to the nearest hospital to assess possible health risks and receive advice on necessary actions.

Ibuprofen overdose
Symptoms of overdose may include nausea, abdominal pain, vomiting (possibly with blood), gastrointestinal bleeding (see also section 4 below), diarrhoea, headache, tinnitus, confusion, and nystagmus. Stimulation, drowsiness, disorientation, or coma may also occur. Seizures may occur sporadically in patients. After large doses, drowsiness, chest pain, palpitations, loss of consciousness, seizures (especially in children), weakness, dizziness, blood in urine, low blood potassium levels, feeling cold, and breathing difficulties have been reported. In addition, prothrombin time (INR) may be prolonged, probably due to impaired blood clotting factor function. Acute kidney failure and liver damage may occur. In patients with asthma, worsening of asthma symptoms may occur. In addition, low blood pressure and breathing difficulties may occur.

Paracetamol overdose
Accidental or intentional overdose may cause symptoms within a few to several hours, such as pallor, nausea, vomiting, anorexia, excessive sweating, drowsiness, and general weakness. These symptoms may subside the next day, even though liver damage may have started to develop, which later becomes apparent as upper abdominal discomfort, recurrence of nausea, and jaundice.

Missed dose of Metafen
If a dose is missed and symptoms persist, take the next dose as scheduled. Do not take a double dose to make up for the missed dose.

Stopping Metafen
If you have any further questions about using 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.

Common adverse effects (occur in less than 1 in 10 patients):

• abdominal pain, diarrhoea, indigestion, nausea, gastric discomfort and vomiting;
• increased activity of alanine aminotransferase and gamma-glutamyl transferase, and altered liver function test parameters (following paracetamol administration), increased blood creatinine and urea levels.

Uncommon adverse effects (occur in less than 1 in 100 patients):

• headache and dizziness; flatulence, constipation;
• peptic ulcer, gastrointestinal perforation or bleeding, with symptoms such as black tarry stools and vomiting of blood, sometimes with fatal outcome, particularly in elderly patients;
• ulcerative stomatitis and exacerbation of ulcerative colitis and Crohn's disease; pancreatitis has been reported less frequently;
• various types of skin rash, including itching and urticaria, angioedema and facial swelling;
• increased activity of aspartate aminotransferase, increased alkaline phosphatase, creatine phosphokinase and blood creatinine levels, decreased haemoglobin concentration and increased platelet count.

Rare adverse effects (occur in less than 1 in 1,000 patients):

• gastric mucosal inflammation;
• oedema.

Very rare adverse effects (occur in less than 1 in 10,000 patients):

• blood disorders (agranulocytosis, anaemia, aplastic anaemia, haemolytic anaemia, leukopenia, neutropenia, pancytopenia and thrombocytopenia) – initial symptoms include fever, sore throat, superficial ulceration of the oral mucosa, influenza-like symptoms, severe fatigue, unexplained bleeding and bruising, and nosebleeds;
• photosensitivity reactions have been reported. These may manifest as non-specific allergic reactions and anaphylaxis; severe hypersensitivity reactions (anaphylaxis, angioedema) – symptoms include swelling of the face, tongue and larynx, shortness of breath, rapid heartbeat, hypotension – if these occur, contact a doctor immediately;
• confusion, depression and hallucinations;
• paraesthesia (numbness, tingling in limbs), optic neuritis and somnolence, restlessness, irritability;
• in patients with pre-existing autoimmune diseases (systemic lupus erythematosus, mixed connective tissue disease), isolated cases of aseptic meningitis have been reported during ibuprofen treatment, with symptoms such as neck stiffness, headache, nausea, vomiting, fever and disorientation;
• depression, psychotic reactions and tinnitus (isolated cases reported);
• visual disturbances;
• tinnitus and vertigo of labyrinthine origin;
• bronchial asthma, worsening of asthma, bronchospasm and dyspnoea (symptoms of respiratory hypersensitivity – see section 2);
• abnormal liver function, hepatitis and jaundice, enlarged liver; acute liver failure, liver failure, liver necrosis and liver damage (following paracetamol overdose);
• excessive sweating, purpura; very rare cases of severe skin reactions have been reported – exfoliative dermatitis; bullous reactions, including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis (see section “Warnings and precautions”);
• nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, and acute and chronic renal failure, painful urination, reduced urine output, increased serum urea concentration, increased serum sodium concentration (sodium retention);
• fatigue and malaise. With the use of NSAIDs at high doses, cases of oedema, hypertension and heart failure have been reported. Clinical studies and epidemiological data suggest that the use of ibuprofen, particularly long-term and at high doses (2400 mg per day), may be associated with a small increased risk of arterial thromboembolic events (e.g. myocardial infarction or stroke).

Adverse effects with unknown frequency (frequency cannot be estimated from available data):

• severe skin reactions known as DRESS syndrome may occur. Symptoms of DRESS syndrome include: skin rash, fever, lymphadenopathy and increased eosinophil count (a type of white blood cell); red scaly rash with subcutaneous nodules and blisters, predominantly located in skin folds, trunk and upper limbs, with fever occurring early in treatment (acute generalised exanthematous pustulosis). If such symptoms occur, discontinue Metafen immediately and seek medical help without delay. See also section 2.
• skin becomes sensitive to light.
• a serious condition that may cause blood acidification (so-called metabolic acidosis) in patients with severe illness taking paracetamol (see section 2).

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse effects 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
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Metafen

Do not store above 25°C.
Keep the medicine in a place out of sight and out of reach of children.
Do not use this medicine after the expiry date stated on the blister or carton following: EXP.
The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Metafen contains

• The active substances in this medicine are: ibuprofen and paracetamol. Each coated tablet contains 200 mg of ibuprofen and 325 mg of paracetamol.
• Other ingredients are:
• pregelatinized starch, maize; microcrystalline cellulose; povidone K-90; povidone K-29/32; magnesium stearate;
• coating: polyvinyl alcohol; titanium dioxide (E 171); macrogol 3350; talc.

What Metafen looks like and contents of the pack
The medicine is in the form of white or almost white, oval, film-coated tablets, with the inscription
"Metafen" embossed on one side. The tablets have a length of 18.2 mm ± 0.3 mm and a width of 8.2 mm ± 0.3 mm.
Outer packaging – cardboard box, containing respectively:
2, 6, 10, 20, or 60 film-coated tablets in PVC/aluminum blisters.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01