Package leaflet: Information for the user

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

Table of contents

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

1. What Hadmuliv is and what it is used for

Hadmuliv 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.
Hadmuliv is used for the short-term symptomatic treatment of mild to moderate pain.
It is particularly suitable for treating pain that has not responded to ibuprofen or paracetamol taken separately.
Hadmuliv is intended for adults aged 18 years and over.

2. Important information before using Hadmuliv

When not to use Hadmuliv:

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 ulcer 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 therapy,
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 insufficient 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 Hadmuliv, 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 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 is prone to bleeding,
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 organ dysfunction or other mixed 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 disorders of certain enzymes presenting with neurological complications or skin problems, or sometimes both, i.e. porphyria,
the patient has haemolytic anaemia,
the patient has hay fever, nasal polyps, or chronic obstructive pulmonary disease,
as there may be an increased risk of allergic reactions,
the patient suffers from chronic alcoholism,
the patient is underweight or chronically undernourished,
the patient has a lack of total body water (dehydration),
the patient has recently undergone major surgery,
the patient is in the first 6 months of pregnancy or is breastfeeding,
the patient is planning pregnancy,
Consult a doctor if any of the above warnings currently apply 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 time needed to relieve symptoms. Do not use Hadmuliv for longer than 3 days.
Concomitant use with NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, increases the risk of adverse effects (see below "Hadmuliv and other medicines") and should be avoided.
During treatment with Hadmuliv, inform the doctor immediately:
If the patient has severe conditions, 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 (a blood and fluid imbalance) has been reported in patients taking regular doses of paracetamol over a prolonged period or taking paracetamol 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 pain relief but is associated with the 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 Hadmuliv"). 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 Hadmuliv".
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 if used in high doses. Do not exceed the recommended dose or duration of treatment.
Before starting treatment with Hadmuliv, discuss with a doctor or pharmacist if the patient:

has heart disease, including heart failure, angina (chest pain), 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.

Skin reactions
Severe skin reactions associated with the use of Hadmuliv 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
Hadmuliv may mask symptoms of infection, such as fever and pain. Therefore, Hadmuliv 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 symptoms persist or worsen, consult a doctor immediately.
Gastrointestinal symptoms
Serious adverse effects on the gastrointestinal tract (affecting the stomach and intestines) have been reported during the use of NSAIDs, including ibuprofen. 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 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 headaches may worsen them. 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 salt loss and dehydration. Therefore, this should be avoided.
Vision problems
If any vision problems occur after taking Hadmuliv, discontinue use and consult a doctor.
Other notes
Generally, habitual use of painkillers, especially in combination with multiple pain-relieving active substances, may lead to permanent kidney damage with risk of kidney failure. Therefore, this should be avoided.
Children and adolescents
This medicine is contraindicated in children and adolescents under 18 years of age.
Hadmuliv and 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.
Do not use Hadmuliv with:

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

Exercise particular caution, as some medicines may interact with Hadmuliv, 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),
anticoagulant medicines (i.e. blood thinners/anti-thrombotics, e.g. warfarin, acetylsalicylic acid, ticlopidine),
cardiac glycosides (e.g. digoxin), heart-strengthening medicines,
medicines used to treat high cholesterol (e.g. cholestyramine),
diuretic medicines (promoting water excretion),
medicines that lower high blood pressure (ACE inhibitors, such as captopril; beta-blockers, such as 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, SSRIs),
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),
ginkgo biloba (herbal remedy) may increase the risk of bleeding during NSAID use,
medicines used to treat tuberculosis (e.g. isoniazid),
flucloxacillin (antibiotic), due to the serious risk of blood and body 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 Hadmuliv or be affected by it. Therefore, before starting treatment with Hadmuliv together with other medicines, the patient should consult a doctor or pharmacist.
Hadmuliv with food and alcohol
To reduce the likelihood of adverse effects, take Hadmuliv 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 child, she should consult a doctor or pharmacist before using this medicine.

Pregnancy Do not take Hadmuliv during the last 3 months of pregnancy, as it may harm the unborn child or cause delivery complications. It may cause kidney and heart problems in the unborn child. It may affect bleeding tendency in both mother and child and may cause delayed or prolonged labour. Do not take Hadmuliv during the first 6 months of pregnancy unless absolutely necessary and prescribed 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 Hadmuliv is used for longer than a few days beyond week 20 of pregnancy, it may cause kidney problems in the unborn child, leading 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 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 used during breastfeeding if taken at the recommended dose and for the shortest possible duration.
Fertility Ibuprofen belongs to a group of medicines that may impair fertility in women. Hadmuliv may make it more difficult to become pregnant. This effect is reversible after stopping the medicine.

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

3. How to use Hadmuliv

This medicine should always be used exactly as described in this patient 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 must be maintained between doses.
Do not take more than 6 tablets in 24 hours (corresponding to 1200 mg of ibuprofen and 3000 mg of paracetamol per day).
It is recommended to take Hadmuliv 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 Hadmuliv (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 worsen, consult a doctor immediately (see section 2).

Taking more Hadmuliv than recommended
If a patient takes more Hadmuliv than recommended, or if the medicine is accidentally taken by a child, contact a doctor or the nearest hospital immediately for advice on potential risks and necessary actions.

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. Excitement, 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 peripheral and central dizziness may occur. Hematuria (blood in urine), hypokalemia (low blood potassium), cold sensation, and breathing difficulties may also occur. Prothrombin time/INR may be prolonged, likely due to impaired coagulation factor function in circulation. Acute renal failure and liver damage may occur. In patients with asthma, worsening of asthma is possible. Additionally, low blood pressure, shallow breathing, and blue-red discoloration of the skin and mucous membranes (cyanosis) may occur.

If a dose higher than recommended has been taken, seek immediate medical advice even if the patient feels well. An excessive dose of paracetamol may cause delayed, severe liver damage, which can be fatal. Even in the absence of discomfort or poisoning symptoms, urgent medical care may be required. Liver damage may become irreversible if treatment is delayed. To prevent liver damage, treatment must be initiated as early as possible.

Missed dose of Hadmuliv
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 then take the next dose after at least 6 hours have passed.

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.
The following adverse reactions should be considered as being largely dose-dependent and varying between patients.
The most commonly observed adverse reactions are gastrointestinal in nature. Gastrointestinal ulcers, perforation or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients. After administration, nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, 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.

Treatment with NSAIDs has been associated with oedema, high blood pressure and heart failure.

STOP TAKING the medicine and inform your doctor if the patient experiences:
Uncommon (may occur in less than 1 in 100 people)
symptoms of gastrointestinal bleeding (severe abdominal pain, blood in vomit or stools, black tarry stools).

Very rare (may occur in less 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 may occur, accompanied by fever, drowsiness, diarrhoea and nausea) 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 not known (frequency cannot be estimated from available data)
severe skin reactions described as DRESS syndrome (frequency not known). Symptoms of DRESS syndrome include: skin rash, fever, lymph node swelling 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 at the beginning of treatment (acute generalised exanthematous pustulosis). If such symptoms occur, stop taking the medicine and seek medical help immediately. See also section 2;
serious condition which may cause the blood to become more acidic (so-called metabolic acidosis) in patients with severe illness taking paracetamol (see section 2).

Other possible adverse reactions:
Common (may occur in less than 1 in 10 people):
gastrointestinal disorders such as abdominal pain, heartburn, dyspepsia, nausea, vomiting, flatulence and constipation, diarrhoea, minor blood loss from the gastrointestinal tract, which in rare cases may lead to anaemia;
increased alanine aminotransferase activity, increased gamma-glutamyltransferase activity and abnormal liver function tests after administration of paracetamol;
oedema and fluid retention, swelling of ankles or legs (oedema); fluid retention usually resolves quickly upon discontinuation of combination therapy;
elevated blood creatinine and urea levels.

Uncommon (may occur in less 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);
thickening of respiratory tract mucus;
rashes of various types;
gastrointestinal ulcers, potentially with bleeding and perforation or gastrointestinal bleeding, exacerbation of inflammatory bowel conditions (colitis) 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 occur in less than 1 in 1,000 people)
sleep disturbances;
kidney tissue damage (especially with long-term use);
high uric acid levels in blood (hyperuricaemia);
abnormal skin sensation (tingling, pins and needles).

Very rare (may occur in less 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 exhaustion, 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 Hadmuliv and consult a doctor;
hearing loss, tinnitus, sensation of spinning (dizziness), confusion, psychotic reactions, hallucinations, depression;
fatigue, general malaise;
increased sweating, photosensitivity, exfoliative dermatoses;
red, blotchy 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, liver function disturbances, liver necrosis and liver damage;
nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, and acute and chronic renal 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 not known (frequency cannot be estimated from available data)
skin photosensitivity.

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

Reporting of adverse reactions
If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, consult a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at 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 reactions can also be reported to the marketing authorisation holder.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Hadmuliv

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box and blister pack following "EXP". The expiry date refers to the last day of the stated month.
Store in the original packaging to protect from light.
No special temperature storage requirements for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such practices help protect the environment.

6. Contents of the pack and other information

What the medicine contains

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

What the medicine looks like and contents of the pack
Hadmuliv is a white or almost white, oval coated tablet measuring 19.7 mm x 9.2 mm.
The coated tablets are packed in PVC/PVDC/Aluminium foil 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
PO Box 3012
41 500 Larissa
Greece
Lek d.d.
Verovškova Ulica 57
1526 Ljubljana
Slovenia

This medicine is authorised in the Member States of the European Economic Area under the following names:
Poland: Hadmuliv
Hungary: Ibuprofen/Paracetamol Sandoz 200 mg/500 mg filmtabletta

For more detailed information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
tel. 22 209 70 00