Package leaflet: information for the patient

ZEUSEFF 500 mg + 30 mg effervescent tablets

paracetamol + codeine phosphate
Generic medicine
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What ZEUSEFF is and what it is used for

ZEUSEFF contains two active substances (paracetamol and codeine), which act in different ways.
Paracetamol works by relieving pain (analgesic) and reducing fever (antipyretic).
Codeine belongs to a group of medicines called opioid analgesics, which act by relieving pain.
Codeine may be used alone or, as in this medicine, in combination with other analgesics such as paracetamol.
ZEUSEFF is indicated in patients over 12 years of age for the treatment of symptoms of moderate acute pain that does not respond to treatment with other pain-relieving medicines such as paracetamol or ibuprofen used alone.
Consult your doctor if you do not feel better or if you feel worse.

2. What you need to know before taking ZEUSEFF

Do not take ZEUSEFF
If:

you are allergic to paracetamol or propacetamol hydrochloride (a precursor of paracetamol), codeine, or any of the other ingredients of this medicine (listed in section 6),
you are under 12 years of age,
you suffer from a lung disease (respiratory failure), as codeine may worsen your condition,
you are between 0 and 18 years old and have undergone surgery to remove your tonsils and/or adenoids due to a breathing disorder called obstructive sleep apnoea syndrome,
you have a liver enzyme that causes your body to convert codeine into high levels of morphine (detected through urine testing), increasing the risk of serious adverse effects,
you are breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
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Talk to your doctor or pharmacist before taking ZEUSEFF.
Consult your doctor if:

you have mild to moderate impairment of liver function (including Gilbert’s syndrome, a condition characterized by excessive production of bilirubin, a substance causing yellowing of the skin and eyes),
you have severe liver problems,
you suffer from acute hepatitis (acute inflammation of the liver),
you are taking medicines that stimulate liver enzymes (increasing liver activity),
you have glucose-6-phosphate dehydrogenase deficiency (a substance normally present in the human body; deficiency may cause haemolytic anaemia),
you suffer from haemolytic anaemia (a disease caused by destruction of blood cells, specifically red blood cells),
you suffer from renal failure (kidney disease),
you chronically consume alcohol or drink excessively (3 or more alcoholic drinks per day),
you suffer from anorexia (an eating disorder characterized by lack or reduced appetite),
you suffer from bulimia (an eating disorder in which a person consumes excessive amounts of food and then uses various methods to eliminate it to avoid weight gain),
you suffer from cachexia (a state characterized by extreme thinness, reduced muscle mass, and thinning skin due to chronic illness),
you suffer from chronic malnutrition,
you suffer from dehydration (severe loss of water/fluids from the body),
you suffer from hypovolaemia (reduced volume of circulating blood),
you have a cough with phlegm. Paracetamol may cause severe skin reactions which can be fatal. Use of ZEUSEFF must be discontinued at the first sign of skin rash or any other sign of hypersensitivity (allergic reaction). Opioid therapy may cause:
respiratory depression (reduced breathing function) and sedation
lowered seizure threshold (i.e., increased excitability of the nervous system, as in epilepsy)
hyperalgesia (increased sensitivity to pain), constipation (difficult or infrequent bowel movements)
nausea and vomiting
masking of symptoms of acute abdominal conditions (conditions characterized by severe pain and signs of abdominal irritation)
obstruction of bile and pancreatic juice outflow, as in certain biliary tract diseases, for example pancreatitis (inflammation of the pancreas) and cholelithiasis (presence of gallstones in the gallbladder)
increased histamine release, as in asthma (obstruction of the airways)
pruritus (itching)
reduced hormone levels
inhibition of immunological function (i.e., suppression of the body's defence system)
muscle rigidity and myoclonus (involuntary rapid muscle jerks)
urinary retention (difficulty emptying the bladder), particularly in patients with urethral narrowing (the final part of the urinary tract) or enlarged prostate.

Use of high doses and/or prolonged use
Prolonged or high-dose use of paracetamol may cause liver disease (hepatopathy) and serious adverse effects on the kidneys and blood.
ZEUSEFF – AIC 042710018
Prolonged use of analgesics, including opioids, increases the risk of medication-overuse headache. Additionally, in elderly patients, prolonged use may worsen pre-existing conditions.
With prolonged opioid use, reduced analgesic effectiveness (tolerance) may occur.
Prolonged administration of codeine or doses higher than therapeutic may lead to physical and psychological dependence (addiction) and withdrawal syndrome following sudden discontinuation, which may occur both in patients and in newborns born to codeine-dependent mothers. ZEUSEFF should be used with caution in patients with dependence or a history of opioid dependence, and alternative analgesic therapies should be considered.
Elderly patients
Elderly patients may be at increased risk of adverse effects associated with opioid use, such as respiratory depression and constipation.
Children and adolescents
Do not give codeine for pain relief in children and adolescents after removal of tonsils or adenoids due to obstructive sleep apnoea syndrome.
Children and adolescents should be closely monitored for signs of central nervous system depression associated with codeine, such as extreme drowsiness and respiratory depression.
Codeine is not recommended in children and adolescents with respiratory disorders, as symptoms of morphine toxicity may be more severe.

Other medicines and ZEUSEFF
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are taking:

other medicines containing paracetamol, as serious adverse effects may occur if paracetamol is taken in high doses
other medicines containing opioids or other substances that depress the central nervous system, to avoid the risk of overdose or serious adverse effects
coumarin anticoagulants including warfarin (medicines that delay blood clotting): your doctor will perform more frequent monitoring of INR values (the time it takes for blood to clot)
medicines or substances that stimulate liver enzymes (increasing liver activity), for example:
- rifampicin (an antibiotic)
- cimetidine (a medicine used to treat stomach ulcers)
- antiepileptics (medicines used to treat epilepsy), such as glutethimide, phenobarbital, carbamazepine, and phenytoin. If you are being treated with phenytoin, do not take high or prolonged doses of paracetamol.
- use of these medicines with ZEUSEFF requires extreme caution and must be done only under strict medical supervision.
probenecid, a medicine used to treat hyperuricaemia (high blood uric acid levels) and gout (joint inflammation due to uric acid deposits): your doctor may advise you to reduce the dose of ZEUSEFF.
salicylamide (a pain-relieving and fever-reducing medicine)
flucloxacillin (an antibiotic): your doctor will monitor you more closely for possible onset of a condition causing increased acid levels in the blood (metabolic acidosis)
chloramphenicol (an antibiotic): may increase the risk of possible adverse effects
medicines that slow stomach emptying, such as anticholinergics: these medicines delay the effect of ZEUSEFF.
zidovudine (a medicine for the treatment of HIV)

ZEUSEFF – AIC 042710018

strong painkillers (buprenorphine, butorphanol, nalbuphine, nalorphine, pentazocine)
naltrexone (a medicine for treating drug dependence)
antihistamines (medicines for treating allergies)
analgesics (alfentanil, dextromoramide, dextropropoxyphene, fentanyl, dihydrocodeine, hydromorphone, morphine, oxycodone, pethidine, phenoperidine, remifentanil, sufentanil, tramadol)
cough medicines (dextromethorphan, noscapine, pholcodine, codeine, ethylmorphine)
medicines for psychiatric disorders (chlorpromazine, haloperidol, levomepromazine, thioridazine)
methadone (a medicine for treating drug dependence)
meprobamate (a medicine for treating anxiety)
benzodiazepines and barbiturates (medicines for treating insomnia and anxiety)
medicines for treating depression (paroxetine, fluoxetine, bupropion, sertraline, imipramine, clomipramine, amitriptyline, nortriptyline, doxepine, mirtazapine, mianserin, trimipramine, and monoamine oxidase inhibitors)
antihypertensives (medicines for treating high blood pressure)
baclofen, a medicine to reduce and relieve muscle spasms (excessive muscle tension occurring in various diseases)
thalidomide, a medicine for treating multiple myeloma (a disease of the immune system, the body's defence system)
celecoxib (a medicine that relieves inflammation)
quinidine (a medicine for treating irregular heart rhythm)
dexamethasone (a medicine for treating various disorders such as inflammation and allergies)
anticholinergics (medicines for treating various conditions such as bladder problems, allergies, and depression).
Concomitant use of ZEUSEFF and sedative medicines, such as benzodiazepines or related drugs, increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use should only be considered when no other treatment options are available. However, if your doctor prescribes ZEUSEFF together with sedative medicines, the dose and duration of concomitant treatment must be limited by the doctor. Inform your doctor about all sedative medicines you are taking and follow the doctor’s dosage recommendations carefully. It may be helpful to inform friends or relatives so they are aware of the above-mentioned signs and symptoms. Contact your doctor if you experience such symptoms.

Laboratory tests and ZEUSEFF
If you need to undergo blood tests, keep in mind that paracetamol administration may interfere with the measurement of uric acid levels (uricaemia) and blood glucose levels (glycaemia).
ZEUSEFF and alcohol
Concomitant use of alcohol and codeine may enhance the sedative effect: alcohol consumption during treatment with ZEUSEFF is not recommended.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor or pharmacist before taking this medicine.
If necessary, ZEUSEFF may be used during pregnancy. It is advisable to use the lowest possible dose that relieves pain and/or fever and to take it for the shortest possible duration.
Contact your doctor if pain and/or fever do not decrease and if you need to take the medicine more frequently.
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Pregnancy
Paracetamol
Clinical experience with paracetamol use during pregnancy is limited.
Codeine
Available data are insufficient to exclude an association between congenital malformations and codeine use during pregnancy.
Maternal use of codeine at any stage of pregnancy may be associated with planned caesarean delivery. Use in the third trimester may be associated with an increased risk of emergency caesarean section, postpartum haemorrhage, and possible onset in the newborn of opioid withdrawal symptoms including restlessness, excessive crying, tremors, increased muscle tone (hypertonia), increased respiratory rate (tachypnoea), fever (pyrexia), vomiting, and diarrhoea.
Breastfeeding
Do not take ZEUSEFF if you are breastfeeding. Codeine and morphine pass into breast milk.
Driving and using machines
ZEUSEFF may affect your ability to drive vehicles or operate machinery, as it may cause adverse effects such as drowsiness and cognitive disturbances, including impaired attention.
ZEUSEFF effervescent tablets contain:
✓ sodium: this medicine contains 349 mg of sodium (a main component of table salt) per effervescent tablet. This corresponds to approximately 17% of the maximum recommended daily dietary intake for an adult. Speak with your doctor or pharmacist if you need one or more doses per day for a prolonged period, especially if you have been advised to follow a low-sodium diet;
✓ aspartame (E951): this medicine contains 30 mg of aspartame per effervescent tablet. Aspartame is a source of phenylalanine. It may be harmful if you have phenylketonuria, a rare genetic disorder causing accumulation of phenylalanine because the body cannot properly metabolize it;
✓ sorbitol: this medicine contains 252 mg of sorbitol per effervescent tablet. Sorbitol is a source of fructose. If your doctor has informed you that you (or your child) are intolerant to certain sugars, or if you have been diagnosed with hereditary fructose intolerance, a rare genetic disorder in which patients cannot metabolize fructose, consult your doctor before you (or your child) take this medicine.

3. How to take ZEUSEFF

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
To avoid the risk of overdose, check that other medicines you are taking (with or without a prescription)
do not contain paracetamol or codeine.
Accidental ingestion of an excessive dose of paracetamol may cause severe liver damage
and death (see section If you take more ZEUSEFF than you should).
Adults and adolescents aged 12 years and over with body weight above 60 kg
The recommended dose is 1 or 2 tablets, depending on the intensity of pain, taken 1 to 3
times daily at intervals of at least 6 hours.
Adolescents aged 12 years and over with body weight below 60 kg
Dosage should be determined according to body weight.
The recommended dosage is 1 tablet per administration, up to a maximum of 4
tablets per day, at intervals of at least 6 hours.
ZEUSEFF – AIC 042710018
Children under 12 years of age
Do not give ZEUSEFF to children under 12 years of age.
Patients with kidney disease
If you suffer from severe kidney disease, the interval between doses should be at least 8
hours.
Patients with liver disease
If you have impaired liver function, the dose should be reduced or the interval between doses prolonged.
The maximum dose must not exceed 4 tablets per day in the following cases:
adult patients weighing less than 50 kg, liver disease, Gilbert's syndrome, chronic alcoholism,
chronic malnutrition, or dehydration.
Elderly patients
The initial dose should be half of the recommended adult dose and may be
increased subsequently based on tolerability.
Duration of treatment
This medicine should not be taken for more than 3 consecutive days. If pain does not improve after 3
days, consult your doctor.
Method of administration
For oral use. Dissolve the effervescent tablet in a glass of water and drink
the solution immediately. Do not swallow or chew the effervescent tablet.
If you take more ZEUSEFF than you should
In case of accidental ingestion/overdose of ZEUSEFF, contact your doctor immediately
or go to the nearest hospital.
Paracetamol
Taking an excessive dose of paracetamol increases the risk of poisoning and may lead
to death, especially if:

you have liver disease
you abuse alcohol
you suffer from chronic malnutrition
you are taking medicines or substances that stimulate liver enzymes (increasing liver metabolism).
Symptoms that may occur within the first 24 hours after ingestion of very high doses of paracetamol include:
nausea
vomiting
anorexia (loss or reduction of appetite)
pallor
malaise
diaphoresis (excessive sweating)
Ingestion of 7.5 g or more of paracetamol in adults and 140 mg per kg of body weight in children may result in severe liver damage, leading to abnormal blood test results (ALT, AST, lactate dehydrogenase, bilirubin, prothrombin), coma (a deep state of unconsciousness), or death. Symptoms of liver damage peak after 3–4 days. Codeine The maximum dose of opioids varies from individual to individual. An overdose of codeine or other opioids may primarily cause:

ZEUSEFF – AIC 042710018

respiratory depression ranging from decreased respiratory rate to apnea (absence of breathing)
extreme sedation ranging from drowsiness to coma
miosis (constriction of the pupils)
Other symptoms related to central nervous system effects may also occur, including:
headache
vomiting
urinary retention (difficulty emptying the bladder)
reduced intestinal motility (peristalsis)
bradycardia (reduced heart rate)
hypotension (low blood pressure).

Treatment
The doctor will provide appropriate supportive therapy based on the nature and severity of symptoms.
If you forget to take ZEUSEFF
Do not take/give the adolescent a double dose to make up for a forgotten dose.
If you stop taking ZEUSEFF
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
STOP taking this medicine and contact your doctor immediately if you/your adolescent experience any of the following side effects:

Skin reactions that may present as:
- itching
- urticaria (appearance of itchy skin welts)
- skin rash
- erythema (redness of the skin)
- erythema multiforme (appearance of red spots on the skin with a "target-like" appearance, associated with itching)
- Stevens-Johnson syndrome (a serious skin illness characterized by eruptions and skin peeling)
- toxic epidermal necrolysis (a severe skin disease characterized by redness, blistering lesions, and areas of skin detachment and death)
- generalized exanthematous pustulosis (an eruption of hundreds of superficial pustules spread across the entire body)
Allergic reactions that may present as:
- laryngeal edema (swelling of the throat)
- angioedema (swelling of hands, feet, ankles, face, lips, tongue and/or throat)
- hypotension (low blood pressure)
- anaphylactic shock (a severe allergic reaction)
- hypersensitivity
respiratory depression (reduced respiratory activity).

Additionally, the following side effects may occur, for which there are insufficient data available to determine frequency:

anaemia (reduction in haemoglobin in the blood, the substance that carries oxygen)
thrombocytopenia (reduction in the number of platelets in the blood)
leucopenia/agranulocytosis/neutropenia (reduction in the number of white blood cells in the blood)
abnormal liver function
hepatitis (inflammation of the liver)
biliary colic (severe pain in the upper abdomen)
dizziness
somnolence
vertigo
myoclonus (sudden involuntary muscle jerk)
paresthesia (tingling)
syncope (transient loss of consciousness)
tremor
sedation
confusion
drug abuse
drug dependence
hallucination
euphoria (excitement)
dysphoria (depressed mood with irritability and nervousness)
acute renal failure (reduced kidney function)
interstitial nephritis (inflammation of the kidneys)
haematuria (blood in the urine)
anuria (cessation or reduction in urine production by the kidneys)
urinary retention (inability of the bladder to empty completely)
diarrhoea
abdominal pain
nausea
vomiting
constipation
gastrointestinal reactions
pancreatitis (inflammation of the pancreas)
dyspnoea (difficulty breathing)
increased liver enzymes
decrease or increase in INR (a value used to express the time taken for blood to clot)
rhabdomyolysis (severe muscle damage)
asthenia (weakness)
malaise
miosis (constriction of the pupils)
oedema (swelling due to fluid accumulation)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly through the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store ZEUSEFF

Keep this medicine out of the sight and reach of children.
Store the medicine in the original packaging to protect it from moisture.
Do not store above 25°C.
Do not use this medicine after the expiry date stated on the carton after "EXP".
ZEUSEFF – AIC 042710018
The expiry date refers to the last day of that month.
After first opening, use within 3 months.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ZEUSEFF contains

The active substances are: paracetamol and codeine phosphate. Each effervescent tablet contains 500 mg of paracetamol and 30 mg of codeine phosphate.
The other components are: citric acid, sodium hydrogen carbonate, sodium carbonate anhydrous, sodium docusate, sorbitol ( E420 ), aspartame ( E951 ), orange flavour, lemon flavour, simethicone.

Description of the appearance of ZEUSEFF and contents of the pack
ZEUSEFF is presented as effervescent tablets, white, flat, with a break line.
It is available in packs of 16 tablets in a bottle containing silica gel as a desiccant in the cap.
Marketing Authorization Holder
Omikron Italia S.r.l.
Via Flaminia Nuova, 1068
00189 Rome (Italy)
Manufacturer
E-Pharma Trento S.p.A.
Frazione Ravina
Via Provina, 2
38123 Trento (TN)