Package leaflet: Information for the user

Kivenul, 200 mg + 500 mg, film-coated tablets
Ibuprofenum + Paracetamolum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.
This medicine should always be taken exactly as described in this patient leaflet or
as directed by your doctor or pharmacist.

Keep this leaflet, as you may need to read it again.
If you need advice or further information, consult your pharmacist.
If you experience any side effects, including any possible side effects not listed in this leaflet, tell your doctor or pharmacist. See section 4.
If there is no improvement after 3 days, or if you feel worse, you should contact your doctor.

Contents of the leaflet

What Kivenul is and what it is used for
What you need to know before taking Kivenul
How to take Kivenul
Possible side effects
How to store Kivenul
Contents of the pack and other information

1. What Kivenul is and what it is used for

Kivenul contains two active substances (the components responsible for the medicine's action):
ibuprofen and paracetamol.
Ibuprofen belongs to a group of medicines known as non-steroidal anti-inflammatory drugs (NSAIDs).
Paracetamol works differently from ibuprofen, but both active substances act together to reduce pain.
Kivenul is used for short-term symptomatic treatment of mild to moderate pain.
It is particularly suitable for treating pain that has not responded to ibuprofen or paracetamol used separately.
Kivenul is intended for adults aged 18 years and over.

2. Important information before using Kivenul

When not to use Kivenul:

if the patient is allergic to ibuprofen, paracetamol, or any of the other ingredients of this medicine (listed in section 6),
if the patient is already taking any other medicine containing paracetamol,
if the patient has experienced allergic reactions (e.g. bronchospasm, angioedema, asthma, rhinitis, or urticaria) associated with the use of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs),
if the patient has active or recurrent peptic disease (e.g. gastric or duodenal ulcers) or gastrointestinal bleeding (two or more episodes of confirmed ulceration or bleeding),
if the patient has experienced gastrointestinal bleeding or perforation related to previous NSAID treatment,
if the patient has intracranial haemorrhage or other active bleeding,
if the patient has blood coagulation disorders,
if the patient has heart, liver or kidney failure,
if the patient is severely dehydrated, e.g. due to vomiting, diarrhoea or inadequate fluid intake,
if the patient is in the third trimester of pregnancy,
if the patient is under 18 years of age.

Warnings and precautions
Before starting treatment with Kivenul, consult a doctor or pharmacist if:
the patient is elderly,
the patient has or has had asthma,
the patient has kidney, heart, liver or intestinal diseases, hepatitis, or difficulty urinating,
the patient is being treated simultaneously with medicines affecting liver function,
the patient is allergic to other substances,
the patient has heartburn, indigestion, gastric ulcers or any other stomach problems,
the patient has a tendency to bleed,
the patient has been diagnosed with Gilbert's syndrome (a rare inherited metabolic disorder that may present with symptoms such as yellowing of the skin or whites of the eyes),
the patient has been diagnosed with systemic lupus erythematosus – an autoimmune disease affecting connective tissue, causing joint pain, skin changes and disturbances in the function of other organs, or other connective tissue diseases,
the patient has gastrointestinal disorders or chronic inflammatory bowel disease (e.g. ulcerative colitis or Crohn's disease),
the patient has an infection — see below, section titled "Infections",
the patient has a congenital deficiency of an enzyme called glucose-6-phosphate dehydrogenase,
the patient has congenital, genetic or acquired enzyme disorders presenting with neurological or skin complications, or sometimes both, i.e. porphyria,
the patient has haemolytic anaemia,
the patient has hay fever, nasal polyps or chronic obstructive pulmonary disease,
as this may increase the risk of allergic reactions,
the patient suffers from chronic alcoholism,
the patient is underweight or chronically undernourished,
the patient has total body water deficiency (dehydration),
the patient has recently undergone major surgery,
the patient is in the first 6 months of pregnancy or is breastfeeding,
the patient plans pregnancy,
Consult a doctor if any of the above warnings apply currently or have applied in the past. It may be necessary to avoid using this medicine or to reduce the dose.
Adverse effects can be minimized by using the lowest effective dose for the shortest possible duration needed to relieve symptoms. Do not use Kivenul for longer than 3 days.
Concomitant use with NSAIDs, including selective cyclooxygenase-2 inhibitors, increases the risk of adverse effects (see below "Kivenul and other medicines") and should be avoided.
During treatment with Kivenul, inform the doctor immediately:
If the patient has severe diseases, including severe kidney dysfunction or sepsis (when bacteria and their toxins circulate in the blood, leading to organ damage) or malnutrition, chronic alcoholism, or if the patient is also taking flucloxacillin (an antibiotic).
Severe metabolic acidosis (an abnormality in blood and body fluids) has been reported in patients who take paracetamol regularly over a long period or who take paracetamol together with flucloxacillin. Symptoms of metabolic acidosis may include: severe breathing difficulties, including rapid deep breathing, drowsiness, nausea and vomiting.
Warning: taking doses higher than recommended does not result in stronger analgesic effect but is associated with risk of severe liver damage. Therefore, the maximum daily dose of paracetamol must not be exceeded. Do not take other medicines containing paracetamol (see also above "When not to use Kivenul"). Consult a doctor or pharmacist before taking other medicines also containing paracetamol. Symptoms of liver damage usually appear after several days.
Therefore, it is important to seek medical advice immediately after taking a higher dose than recommended. See also section 3 "Overdose of Kivenul".
The use of anti-inflammatory and/or analgesic medicines such as ibuprofen may be associated with a small increased risk of heart attack or stroke, especially when used at high doses. Do not exceed the recommended dose or duration of treatment.
Before starting treatment with Kivenul, discuss with a doctor or pharmacist if the patient:

has heart diseases, including heart failure, angina pectoris (chest pain), or has had a heart attack, coronary artery bypass surgery, peripheral arterial disease (poor circulation in legs or feet due to narrowed or blocked arteries), or any type of stroke (including "mini-stroke" or transient ischaemic attack "TIA");
has high blood pressure, diabetes, high cholesterol levels, a family history of heart disease or stroke, or smokes tobacco.

Skin reactions
Severe skin reactions related to the use of Kivenul have been reported. If any skin rash, mucosal changes, blisters or other allergic symptoms appear, discontinue taking the medicine and seek immediate medical help, as these may be early signs of a very serious skin reaction. See section 4.
Infections
Kivenul may mask symptoms of infection such as fever and pain. Therefore, Kivenul may delay appropriate treatment of infection, thereby increasing 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 ongoing infection and symptoms persist or worsen, consult a doctor immediately.
Gastrointestinal symptoms
During the use of NSAIDs, including ibuprofen, serious adverse effects affecting the gastrointestinal tract (stomach and intestines) have been reported. These may occur with or without warning symptoms. The risk of such adverse effects is higher in patients with a history of gastric or intestinal ulcers, especially if bleeding or perforation has also occurred. The risk of gastrointestinal adverse effects is higher in elderly patients. Discuss any gastrointestinal problems in the patient's history with the doctor and remain alert for any unusual abdominal symptoms, including nausea, vomiting, diarrhoea, constipation, indigestion, abdominal pain, tarry stools or bloody vomit.
Long-term use of painkillers
Long-term use of painkillers for headache may worsen the headache. If this occurs or is suspected, inform the doctor and discontinue treatment.
Regular use of painkillers, particularly in combination with multiple analgesic drugs, may lead to permanent kidney damage with risk of kidney failure, a condition known as analgesic nephropathy. This risk may increase with physical exertion associated with loss of salts and dehydration. Therefore, avoid this.
Eye problems
If any vision problems occur after taking Kivenul, stop using the medicine and consult a doctor.
Other notes
Generally, habitual use of painkillers, particularly in combination with multiple analgesic active substances, may lead to permanent kidney damage with risk of kidney failure. Therefore, avoid this.
Children and adolescents
This medicine is contraindicated in children and adolescents under 18 years of age.
Kivenul and other medicines
Tell the doctor or pharmacist about all medicines currently used, recently used, or planned to be used.
Do not use Kivenul with:

other medicines containing paracetamol, such as some cold and flu remedies or painkillers.

Exercise particular caution, as some medicines may interact with Kivenul, e.g.:

corticosteroids in tablet form,
antibiotics (e.g. chloramphenicol or quinolones),
antiemetic medicines (e.g. metoclopramide, domperidone),
acetylsalicylic acid, salicylates or other NSAIDs (including COX-2 inhibitors such as celecoxib or etoricoxib),
anticoagulants (i.e. blood thinners/preventing clots, e.g. warfarin, acetylsalicylic acid, ticlopidine),
cardiac glycosides (e.g. digoxin), medicines strengthening heart function,
medicines used to treat high cholesterol levels (e.g. cholestyramine),
diuretics (promoting water excretion),
medicines lowering high blood pressure (ACE inhibitors, e.g. captopril; beta-blockers, e.g. atenolol; angiotensin II receptor antagonists, e.g. losartan),
medicines suppressing immune system function (e.g. methotrexate, cyclosporine, tacrolimus),
medicines used to treat mania or depression (e.g. lithium or selective serotonin reuptake inhibitors, SSRI),
mifepristone (used to terminate pregnancy),
phenytoin, a medicine used to prevent seizures in epilepsy,
zidovudine, a medicine used in HIV infection (the virus causing acquired immunodeficiency syndrome),
medicines delaying gastric emptying,
medicines used to treat bacterial infections called aminoglycosides,
medicines used to treat gout called probenecid and sulfinpyrazone,
antifungal medicines inhibiting the liver enzyme CYP2C9 (e.g. voriconazole, fluconazole),
other substances known to affect the liver or induce hepatic microsomal enzymes, such as alcohol and antiepileptic drugs (e.g. carbamazepine, phenobarbital, lorazepam),
medicines used to treat diabetes (sulfonylurea derivatives),
Japanese knotweed (herbal medicine) may increase the risk of bleeding during NSAID use,
medicines used to treat tuberculosis (e.g. isoniazid),
flucloxacillin (an antibiotic), due to serious risk of blood and fluid disorder (called metabolic acidosis with high anion gap), which requires urgent treatment (see section 2).

Some other medicines may also affect the action of Kivenul or be affected by it.
Therefore, before starting treatment with Kivenul together with other medicines, the patient should consult a doctor or pharmacist.
Kivenul with food and alcohol
To reduce the likelihood of adverse effects, Kivenul should be taken with food.
Do not consume alcohol during treatment with this medicine. Alcohol may increase paracetamol hepatotoxicity.
Pregnancy, breastfeeding and fertility
If a woman is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult a doctor or pharmacist before using this medicine.

Pregnancy Do not take Kivenul during the last 3 months of pregnancy, as it may harm the unborn child or cause problems during delivery. It may cause kidney and heart problems in the unborn child. It may affect bleeding tendency in both mother and child and may cause delivery to be later or longer than expected. Do not take Kivenul during the first 6 months of pregnancy unless absolutely necessary and recommended by a doctor. If treatment is required during this period or when trying to conceive, use the lowest dose for the shortest possible time. If Kivenul is used for longer than a few days after the 20th week of pregnancy, it may cause kidney problems in the unborn child, which may lead to low levels of amniotic fluid surrounding the child (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the child's heart. If treatment is required for longer than a few days, the doctor may recommend additional monitoring.
Breastfeeding Only a small amount of ibuprofen and its metabolites pass into breast milk. This medicine may be taken during breastfeeding if used at the recommended dose and for the shortest possible duration.
Fertility Ibuprofen belongs to a group of medicines that may impair fertility in women. Kivenul may make it more difficult to become pregnant. This effect is reversible upon discontinuation of the medicine.

Driving and operating machinery
Kivenul may cause dizziness, concentration disturbances and drowsiness. If these symptoms occur, do not drive or operate machinery.

3. How to take Kivenul

This medicine should always be taken exactly as described in this patient information leaflet or as directed by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.
Adults
The recommended dose is 1 tablet up to 3 times daily, taken with water.
A minimum of 6 hours should be maintained between doses.
If symptoms persist after taking 1 tablet, a maximum of 2 tablets may be taken up to 3 times daily. A minimum of 6 hours should be maintained between doses.
Do not take more than 6 tablets within 24 hours (corresponding to 1200 mg of ibuprofen and 3000 mg of paracetamol per day).
It is recommended to take Kivenul with food to reduce the risk of adverse effects.
Use in elderly patients
No special dose adjustment is necessary. However, there is an increased risk of severe adverse effects. The lowest effective dose should be used for the shortest possible duration.
Use in children and adolescents
Do not use in children and adolescents under 18 years of age.
Dose reduction to a maximum of 4 tablets per day may be necessary if:

the patient has kidney problems,
the patient has liver problems,
the patient weighs less than 50 kg,
the patient suffers from chronic malnutrition,
the patient regularly consumes alcohol (chronic alcoholism),
the patient is inadequately hydrated.

If any of the above conditions apply, consult a doctor before taking Kivenul (see also section 2 "Warnings and precautions").
For oral use only and for short-term use only.
Do not use this medicine for longer than 3 days.
If symptoms persist or worsen, consult a doctor.
Use the lowest effective dose for the shortest duration necessary to relieve symptoms. If, during an infection, symptoms (such as fever and pain) persist or intensify, consult a doctor immediately (see section 2).
Taking more Kivenul than recommended
If a patient takes more Kivenul than recommended, or if the medicine is accidentally ingested by a child, contact a doctor or the nearest hospital immediately for advice on potential risks and appropriate management.
Symptoms of overdose may include nausea, abdominal pain, vomiting (possibly with blood), gastrointestinal bleeding (see section 4), diarrhoea, headache, tinnitus, confusion and nystagmus, blurred vision. Stimulation, drowsiness, disorientation or coma may also occur. Seizures have been reported occasionally. After large doses, drowsiness, chest pain, palpitations, loss of consciousness, seizures (mainly in children), weakness and central and peripheral dizziness, presence of blood in urine, low blood potassium levels, feeling cold and breathing difficulties may occur. Additionally, prothrombin time/INR may be prolonged, likely due to impaired coagulation factor function. Acute renal failure and liver damage may also occur. In patients with asthma, worsening of asthma is possible. Furthermore, low blood pressure, shallow breathing and blue-red discoloration of the skin and mucous membranes (cyanosis) may occur.
In case of overdose, seek immediate medical advice even if the patient feels well. Excessive paracetamol intake can cause delayed, severe liver damage, which may be fatal. Even in the absence of discomfort or poisoning symptoms, the patient may require urgent medical treatment. Liver damage may become irreversible if treatment is delayed. To prevent liver damage, prompt treatment is essential.
Missed dose of Kivenul
Do not take a double dose to make up for a missed tablet. If a dose is missed, take it as soon as remembered, and take the next dose no sooner than 6 hours after the previous one.
If you have any further questions 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 following adverse effects are largely dose-dependent and may vary between patients.
The most commonly observed adverse effects are gastrointestinal in nature. Gastrointestinal ulcers, perforation or bleeding, sometimes fatal, may occur, particularly in elderly patients. After administration, nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, black tarry stools, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported. Gastritis has been observed less frequently. In particular, the risk of gastrointestinal bleeding depends on the dose range and duration of treatment.

Fluid retention, high blood pressure and heart failure have been reported in association with NSAID treatment.

STOP TAKING THE MEDICINE and contact a doctor immediately if the patient experiences:

Not very common (may affect fewer than 1 in 100 people):

Signs of gastrointestinal bleeding (severe abdominal pain, blood in vomit or stools, black tarry stools).

Very rare (may affect fewer than 1 in 10,000 people):

Symptoms of aseptic meningitis, such as: neck stiffness, headache, nausea or vomiting, fever, or confusion;
Severe allergic reactions. Symptoms include: swelling of the face, tongue or throat, difficulty breathing, rapid heartbeat, low blood pressure (anaphylaxis, angioedema or severe shock);
Respiratory reactions, including asthma, worsening of asthma, wheezing, difficulty breathing;
Severe skin reactions, such as blistering reactions, including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis;
Worsening of existing severe skin infections (rash, blisters and skin discoloration, fever, drowsiness, diarrhoea and nausea may occur) or worsening of other infections, including chickenpox or shingles, or severe infection with destruction (necrosis) of subcutaneous tissue and muscle, blisters and skin peeling.

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

Severe skin reactions known as DRESS syndrome (frequency unknown). Symptoms of DRESS syndrome include: skin rash, fever, swollen lymph nodes and increased eosinophil count (a type of white blood cell);
Red, scaly rash with subcutaneous nodules and blisters, mainly located in skin folds, trunk and upper limbs, with fever occurring early in treatment (acute generalised exanthematous pustulosis). If such symptoms occur, discontinue the medicine immediately and seek medical help without delay. See also section 2.
Serious condition that may cause blood to become more acidic (so-called metabolic acidosis) in patients with severe illness taking paracetamol (see section 2).

Other possible adverse effects:

Common (may affect fewer than 1 in 10 people):

Gastrointestinal disorders such as abdominal pain, heartburn, dyspepsia, nausea, vomiting, flatulence and constipation, diarrhoea, minor gastrointestinal blood loss which in rare cases may lead to anaemia;
Increased alanine aminotransferase activity, increased gamma-glutamyltransferase activity, and abnormal liver function tests after paracetamol administration;
Oedema and fluid retention, swelling of ankles or legs (oedema); fluid retention usually resolves quickly upon discontinuation of concomitant therapy;
Increased blood creatinine and urea levels;
Increased sweating.

Not very common (may affect fewer than 1 in 100 people):

Central nervous system disorders such as headache, dizziness, insomnia, restlessness, irritability or fatigue;
Urticaria, itching;
Inability to completely empty the bladder (urinary retention);
Thickened respiratory tract mucus;
Various types of skin rash;
Gastrointestinal ulcers, potentially with bleeding and perforation or gastrointestinal bleeding, exacerbation of colitis (inflammatory bowel disease) and gastrointestinal tract (Crohn's disease), ulcerative stomatitis, gastritis;
Decreased haemoglobin and haematocrit levels, increased aspartate aminotransferase activity, increased alkaline phosphatase activity in blood, increased creatine kinase activity in blood, increased platelet count (blood clotting cells).

Rare (may affect fewer than 1 in 1,000 people):

Sleep disturbances;
Kidney tissue damage (especially with long-term use);
High blood uric acid levels (hyperuricaemia);
Abnormal skin sensations (tingling, pins and needles).

Very rare (may affect fewer than 1 in 10,000 people):

Blood disorders (agranulocytosis, anaemia, aplastic anaemia, haemolytic anaemia, leukopenia, neutropenia, pancytopenia and thrombocytopenia).
Initial symptoms include: fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe fatigue, unexplained bleeding, bruising and nosebleeds;
Optic neuritis and drowsiness, aseptic meningitis in patients with pre-existing conditions (such as systemic lupus erythematosus and mixed connective tissue disease), symptoms include neck stiffness, headache, nausea, vomiting, fever or altered consciousness;
Visual disturbances; in such cases, discontinue use of Kivenul and consult a doctor;
Hearing loss, tinnitus, sensation of spinning (dizziness), confusion, psychotic reactions, hallucinations, depression;
Fatigue, general malaise;
Light sensitivity, exfoliative dermatoses;
Red, spotted skin rash (purpura);
Hair loss;
High blood pressure, vasculitis;
Oesophagitis, pancreatitis, formation of diaphragm-like intestinal structures;
Liver problems, dysfunction, liver damage (especially with long-term use), liver failure, acute hepatitis, yellowing of the skin and/or whites of the eyes, also known as jaundice; in overdose, paracetamol may cause acute liver failure, impaired liver function, liver necrosis and liver damage;
Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, and acute and chronic kidney failure;
Fast or irregular heartbeat, also known as palpitations, tachycardia, arrhythmia and other heart rhythm disorders, heart failure (causing shortness of breath, oedema), myocardial infarction.

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

Skin photosensitivity.

Use of medicines such as Kivenul may be associated with a small increased risk of heart attack (myocardial infarction) or stroke (see section 2).

Reporting of adverse effects
If any adverse effects occur, including any possible adverse effects not listed in this leaflet, consult a doctor or pharmacist. 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
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 authorisation holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Kivenul

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and blister after "EXP". The expiry date refers to the last day of the stated month.
Store in the original packaging in order to protect from light.
No special temperature storage conditions apply for this medicine.
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 Kivenul contains

The active substances are ibuprofen and paracetamol. Each coated tablet contains 200 mg of ibuprofen and 500 mg of paracetamol.
The other ingredients are: corn starch, crospovidone (type A), colloidal anhydrous silica, povidone K-30, pregelatinized corn starch, talc and stearic acid (50). Coating: polyvinyl alcohol, talc, macrogol 3350, titanium dioxide (E 171).

What Kivenul looks like and contents of the pack
Kivenul is white or almost white, oval coated tablets with dimensions of 19.7 mm x 9.2 mm.
Coated tablets are packed in PVC/PVDC/Aluminium blisters and placed in a cardboard box.
Pack sizes:
Blisters: 20 coated tablets.
Single-dose blisters: 20 x 1 coated tablet.
Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria
Manufacturer
Rontis Hellas Medical and Pharmaceutical Products S.A.
Larissa Industrial Area,
P.O. Box 3012
Larissa, 41 500
Greece
Lek d.d.
Verovškova Ulica 57
1526 Ljubljana
Slovenia
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Poland Kivenul
Portugal Ibuprofeno + Paracetamol Sandoz
Estonia Ibravix
Lithuania Ibravix 200 mg/500 mg plėvele dengtos tabletės
Latvia Ibravix 200 mg/500 mg apvalkotās tabletes
For more detailed information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warszawa
tel. 22 209 70 00