CO 500 mg/30 mg Effervescent Tablets

Зміст інструкції

1. What is Co-Efferalgan and what is it used for
2. What you need to know before using Co-Efferalgan
3. How to use Co-Efferalgan
4. Possible side effects
5. How to store Co-Efferalgan
6. Package Contents and Other Information
7. What is Co-Efferalgan and what is it used for
8. What you need to know before using Co-Efferalgan
9. How to use Co-Efferalgan
10. Possible side effects
11. How to store Co-Efferalgan
12. Contents of the pack and other information

Co-Efferalgan 500 mg + 30 mg effervescent tablets
paracetamol + codeine phosphate

Read this leaflet carefully before using 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 other people, even if their symptoms are the same as yours, as it could be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Co-Efferalgan is and what it is used for
• 2. What you need to know before you use Co-Efferalgan
• 3. How to use Co-Efferalgan
• 4. Possible side effects
• 5. How to store Co-Efferalgan
• 6. Contents of the pack and other information

1. What is Co-Efferalgan and what is it used for

Co-Efferalgan contains two active ingredients (paracetamol and codeine), which work in different ways.
Paracetamol works by relieving pain (analgesic) and reducing fever (antipyretic).
Codeine belongs to a group of drugs called opioid analgesics that relieve pain.
Co-Efferalgan is indicated in patients over the age of 12for the treatment of symptoms of
moderate acute pain, which does not respond to treatment with other pain relievers such as
paracetamol or ibuprofen used alone.
See your doctor if you do not feel better or if you feel worse.

2. What you need to know before using Co-Efferalgan

Do not use Co-Efferalgan
If:

• you are allergic to paracetamol or propacetamol hydrochloride (a precursor of paracetamol), to codeine or to any of the other ingredients of this medicine (listed in section 6)
• you are less than 12 years old
• 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 removal of tonsils or adenoids because you suffered from a breathing disorder called obstructive sleep apnea syndrome
• you have a liver enzyme that allows your body to convert codeine into a high amount of morphine (detected through urine testing) with a high probability of having serious side effects
• you are breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or pharmacist before using Co-Efferalgan.
Consult your doctor if:

• you suffer from mild/moderate reduction of liver function (including Gilbert's syndrome, a condition characterized by excessive production of bilirubin, a substance that causes a yellowish discoloration of the skin and eyes)
• you suffer from severe liver problems
• you suffer from acute hepatitis (acute inflammation of the liver)
• you are taking medicines that stimulate liver enzymes (increase the way the liver works)
• you suffer from glucose-6-phosphate dehydrogenase deficiency (a substance normally present in the human body, the deficiency of which can cause hemolytic anemia)
• you suffer from hemolytic anemia (a disease due to the destruction of some blood cells, red blood cells)
• you suffer from kidney failure (kidney disease)
• you chronically abuse alcohol. Alcohol consumption during therapy is not recommended
• you suffer from anorexia (an eating disorder characterized by a lack or reduction of appetite)
• you suffer from bulimia (an eating disorder in which a person ingests an excessive amount of food and then resorts to various methods to eliminate it in order not to gain weight)
• you suffer from cachexia (a condition characterized by extreme thinness, reduction of muscle mass and thinning of the skin due to chronic diseases)
• you suffer from chronic malnutrition
• you suffer from dehydration (severe loss of water/fluids from the body)
• you suffer from hypovolemia (reduced blood volume circulating in the body)
• you are in a condition of prolonged fasting
• you have a cough and produce phlegm
• you suffer from or have suffered from opioid, alcohol, prescription drug or illicit substance dependence
• you suffer from a mental disorder (e.g. major depression).

The habitual and prolonged use of codeine (one of the active ingredients of this medicine) can cause
dependence and misuse which can lead to overdose and even death. Do not
take this medicine for longer than necessary. Do not give this medicine to anyone else.
Paracetamol can cause severe skin reactions that can be fatal. The use of Co-Efferalgan
must be stopped at the first appearance of skin rash or any other sign of
hypersensitivity (allergic reaction).
Opioid therapy can cause:

• respiratory depression (reduction of respiratory function) and sedation
• lowering of the convulsive threshold (i.e. increased excitability of the nervous system, as in the case of epilepsy)
• hyperalgesia (increased sensitivity to pain) constipation (difficult or infrequent evacuation)
• nausea and vomiting
• masking of the symptoms of acute abdominal conditions (conditions characterized by severe pain and signs of abdominal irritation)
• obstruction of the outflow of bile and pancreatic juice, as in the case of some diseases of the biliary tract, for example pancreatitis (inflammation of the pancreas) and cholelithiasis (presence of gallstones in the gallbladder)
• increased release of histamine, as in the case of asthma (bronchial obstruction)
• itching
• reduction of hormone levels
• inhibition of immunological function (i.e. the function of the body's defense system)
• muscle rigidity and myoclonus (rapid involuntary muscle twitch)
• urinary retention (difficulty emptying the bladder), especially in patients with narrowing of the urethra (the last tract of the urinary tract) or with enlargement of the prostate.

Use of high doses and/or for prolonged periods
The use of high doses or prolonged use of paracetamol can cause a liver disease
(hepatopathy) and alterations also serious to the kidney and blood.
Prolonged use of analgesics, including opioids, increases the risk of medication overuse headache
(medication overuse headache). Furthermore, in elderly people, prolonged use can worsen a pre-existing condition.
Prolonged use of analgesics (for a period longer than 3 months) in patients with chronic headache
(headache), especially if repeated and frequent, can increase or worsen the headache. In these cases, it is
necessary to consult a doctor.
With prolonged use of opioids, a reduction in analgesic efficacy (tolerance) may occur.
Prolonged administration of codeine or at doses higher than therapeutic doses can give
physical and psychological dependence (habituation) and withdrawal syndrome following sudden
discontinuation of administration which can be observed in both patients and infants born from
codeine-dependent mothers. Co-Efferalgan should be used with caution in patients with dependence
or with a history of opioid dependence, and alternative analgesic therapies should be considered.

Elderly
Elderly patients may be at greater risk of side effects associated with the use of
opioids, such as respiratory depression and constipation.

Children and adolescents
Donot give codeine to relieve pain in children and adolescents after removal of
tonsils or adenoids for obstructive sleep apnea syndrome.
Children and adolescents should be carefully 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 problems, as
the symptoms of morphine toxicity may be worse.

Other medicines and Co-Efferalgan
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
In particular, tell your doctor if you are taking:

• other medicines containing paracetamol, as if paracetamol is taken in high doses, serious side effects can occur
• othermedicines containing opioids or other substances that depress the central nervous system, to avoid the risk of overdose or serious side effects
• coumarin anticoagulants including warfarin(medicines that delay blood clotting): the doctor will carry out more rigorous monitoring of INR values (time it takes for the blood to clot)
• medicines or substances that stimulate liver enzymes (increasing the way the liver works), for example:
• rifampicin (an antibiotic)
• cimetidine (a medicine used in the treatment of stomach ulcers)
• antiepileptics (medicines used to treat epilepsy), for example glutethimide, phenobarbital, carbamazepine and phenytoin. If treated with phenytoin, do not take high doses or prolonged doses of paracetamol.
• The use of these medicines with Co-Efferalgan requires extreme caution and must be carried out only under strict medical supervision.
• probenecid, a medicine used for the treatment of hyperuricemia (high concentration of uric acid in the blood) and gout (inflammation of the joints due to uric acid deposition): the doctor will advise you to reduce the doses of Co-Efferalgan
• salicylamide(a pain reliever and fever reducer)
• flucloxacillin(an antibiotic): the doctor will monitor you more carefully to detect the possible onset of a disorder that increases acids in the blood (metabolic acidosis)
• chloramphenicol(an antibiotic): may increase the risk of possible side effects
• medicines that slow down stomach emptying, such as anticholinergics: these medicines delay the effect of Co-Efferalgan.
• zidovudine(a medicine for the treatment of HIV)
• potent pain relievers(buprenorphine, butorphanol, nalbuphine, nalorphine, pentazocine)
• nalmefene and naltrexone(medicines for treating alcohol and drug dependence, respectively)
• antihistamines(medicines for treating allergies)
• analgesics(alfentanil, destromoramide, destropropoxyphene, fentanyl, dihydrocodeine, hydromorphone, morphine, oxycodone, pethidine, phenoperidine, remifentanil, sufentanil, tramadol)
• medicines for treating cough(dextromethorphan, noscapine, pholcodine, codeine, etymorphine)
• medicines for treating 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)
• medicinesfor treatingdepression(paroxetine, fluoxetine, bupropion, sertraline, imipramine, clomipramine, amitriptyline, nortriptyline, doxepin, mirtazapine, mianserine, trimipramine and monoamine oxidase inhibitors)
• antihypertensives(medicines for treating high blood pressure)
• baclofen, a medicine to reduce and relieve muscle spasms (excessive tension in the muscles that occurs in various diseases)
• thalidomide, a medicine for treating multiple myeloma (a disease of the immune system, the body's defense system)
• celecoxib(a medicine that relieves inflammation)
• quinidine(a medicine for treating irregular heartbeat)
• dexamethasone(a medicine for treating various disorders such as inflammation and allergies)
• anticholinergics(medicines for treating various pathologies such as bladder problems, allergies and depression).

The concomitant use of Co-Efferalgan and sedatives such as benzodiazepines or related medicines
increases the risk of drowsiness, difficulty breathing (respiratory depression), coma and can
endanger the patient's life. For these reasons, concomitant use should be considered
only when alternative treatments cannot be used.
If your doctor prescribes Co-Efferalgan together with sedatives, the dose and duration of treatment
concomitantly must be established by your doctor. Tell your doctor about all the sedatives
you are taking and carefully follow your doctor's recommendations on dosage. It may
be helpful to inform friends or family members to be aware of the onset of the above signs and symptoms.
Contact your doctor when these symptoms occur.

Interference with blood tests
If the person taking the medicine needs to undergo blood tests, keep in mind that the administration of
paracetamol may interfere with the determination of uricemia (the amount of uric acid in the
blood) and glycemia (the amount of sugar in the blood).

Co-Efferalgan and alcohol
The concomitant use of alcohol and codeine can increase the sedative effect: drinking alcohol during
treatment with Co-Efferalgan is not recommended.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning a pregnancy, ask your doctor
or pharmacist for advice before taking this medicine.

Pregnancy
Paracetamol
Clinical experience with the use of paracetamol during pregnancy is limited.
Codeine
The available data are not sufficient to exclude an association between malformations and the use of
codeine during pregnancy.
Maternal use of codeine at any stage of pregnancy may be associated with scheduled cesarean delivery
urgent, postpartum hemorrhage and the possible onset of opioid withdrawal symptoms in the newborn including restlessness, excessive crying, tremors, increased muscle tone (hypertonia), increased respiratory rate (tachypnea), fever (pyrexia), vomiting and
diarrhea.

Breastfeeding
Co-Efferalgan is contraindicated during breastfeeding.

Driving and operating machinery
Co-Efferalgan can affect your ability to drive vehicles or operate machinery as it can cause
side effects such as drowsiness and cognitive impairment, such as attention alteration.

Co-Efferalgan effervescent tablets contains sodium
This medicine contains 384.64 mg of sodium (the main component of table salt) per
tablet. This is equivalent to about 19% of the recommended maximum daily intake in the
diet of an adult. Talk to your doctor or pharmacist if you need one or more doses a day for
a prolonged period, especially if you have been told to follow a low-sodium diet.

Co-Efferalgan effervescent tablets contain aspartame (E951)
This medicine contains 30 mg of aspartame per tablet. Aspartame is a source of
phenylalanine. It may be harmful if you have phenylketonuria, a rare genetic disease that
causes the accumulation of phenylalanine because the body cannot eliminate it correctly.

Co-Efferalgan effervescent tablets contain sorbitol (E420)
This medicine contains 300 mg of sorbitol per tablet, which is equivalent to 300 mg/3250 mg.
Sorbitol is a source of fructose. If your doctor has told you that you (or your child) are intolerant to
certain sugars, or if you have a diagnosis of hereditary fructose intolerance, a rare genetic disease
in which patients cannot metabolize fructose, talk to your doctor before you (or your
child) take this medicine.

Co-Efferalgan effervescent tablets contain sodium benzoate
This medicine contains 58.5 mg of sodium benzoate (E211) per tablet, which is equivalent to
58.5 mg/3250 mg.

Co-Efferalgan effervescent tablets grapefruit flavour, which in turn contains fructose,
glucose and sucrose.
This medicine contains 5 mg of fructose, 5 mg of glucose and 4 mg of sucrose per tablet.
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking
this medicine.

Co-Efferalgan effervescent tablets grapefruit flavour, which in turn contains sulphites
Rarely it may cause severe hypersensitivity reactions and bronchospasm.

Co-Efferalgan effervescent tablets grapefruit flavourcontains 0.5 mg of alcohol (ethanol) per
tablet. The amount per tablet is equivalent to a small amount of beer or wine (trace amounts). The
small amount of alcohol in this medicine will not produce significant effects.

3. How to use Co-Efferalgan

Use this medicine following exactly the instructions of your doctor or pharmacist. If you have
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 intake of an excessive dose of paracetamol can cause serious liver damage
and death (see section If you use more Co-Efferalgan than you should).

Adults and adolescents aged 12 years and over and weighing more than 60 kg
The recommended dose is 1 or 2 tablets, depending on the intensity of the pain, to be taken 1 to 3
times a day at intervals of at least 6 hours.

Adolescents aged 12 years and over and weighing less than 60 kg
The dosage must be determined based on 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.

Children under 12 years of age

Donot give Co-Efferalgan to children under 12 years of age.

Patients with kidney disease
If you suffer from a severe kidney disease, the interval between two administrations must be at least 8
hours.

Patients with liver disease
If you suffer from impaired liver function, the dose must be reduced or the interval between two
administrations prolonged.
The maximum dose should not exceed 4 tablets per day in case of:
adult patients weighing less than 50 kg, liver disease, Gilbert's syndrome, chronic alcoholism,
chronic malnutrition or dehydration.

Elderly
The initial dose should be halved compared to the recommended dosage for adults and may be,
subsequently, increased based on tolerability.

Duration of treatment
The medicine should not be taken for more than 3 days in a row. If the pain does not improve after 3
days, consult your doctor.

Method of administration
Oral use.
Let the effervescent tablet dissolve in a glass of water. Do not swallow or chew.

If you use more Co-Efferalgan than you should
In case of ingestion/accidental intake of an excessive dose of Co-Efferalgan, immediately
inform your doctor or go to the nearest hospital.

Paracetamol
Taking an excessive dose of paracetamol increases the risk of poisoning and can lead
to death, especially if:

• you suffer from liver disease
• you abuse alcohol
• you suffer from chronic malnutrition
• you are taking medicines or substances that stimulate liver enzymes (increasing the way the liver works).

In case of taking very high doses of paracetamol, the symptoms that may appear
within the first 24 hours include

• nausea
• vomiting
• anorexia (loss or reduction of appetite)
• pallor
• malaise
• diaphoresis (profuse sweating).

Following paracetamol overdose, the following have been observed:

• -sudden inability of the kidneys to function properly (acute renal failure),
• - a condition in which small blood clots form in the bloodstream, blocking the smallest blood vessels (disseminated intravascular coagulation),
• rare cases of acute pancreatitis, an inflammation of the pancreas.

In case of ingestion of 7.5 g or more of paracetamol in adults and 140 mg per kg of body weight
in children, serious liver damage may occur with consequent alteration of the results of
some blood tests (AST, ALT, lactic dehydrogenase, bilirubin, prothrombin), coma (deep
state of unconsciousness) or death.
Symptoms of liver damage reach their peak after 3-4 days.

Codeine
The maximum dose of opioids varies from individual to individual.
Taking an excessive dose of codeine or other opioids can primarily lead to:

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

Treatment
The doctor, based on the nature and severity of the symptoms, will carry out the appropriate supportive therapy.

If you forget to use Co-Efferalgan
Do not take/give the adolescent a double dose to make up for a missed dose.

If you stop treatment with Co-Efferalgan
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If you/the adolescent experiences the following side effects STOPtreatment with this
medicine and contact your doctor immediately:

• skin reactions that may manifest with:
• itching
• urticaria (appearance of wheals on the skin accompanied by itching)
• skin rash
• erythema (redness of the skin)
• erythema multiforme (appearance of red spots on the skin with a "bull's-eye" appearance associated with itching)
• purpura (appearance of skin patches of various sizes, purple in color)
• Stevens-Johnson syndrome (severe skin disease with the appearance of rashes and exfoliations)
• toxic epidermal necrolysis (severe skin disease characterized by redness, blistering lesions with areas of detachment and skin death)
• acute generalized exanthematous pustulosis (eruption of hundreds of superficial pustules spread all over the body)
• fixed drug eruption (rash on the skin, red/purple in color)
• allergic reactions that may manifest with:
• laryngeal edema (swelling of the throat)
• angioedema (swelling of hands, feet, ankles, face, lips, tongue and/or throat)
• anaphylactic reaction (severe allergic reaction), including hypotension (low blood pressure)
• anaphylactic shock (severe allergic reaction)
• hypersensitivity
• bronchospasm (excessive and prolonged contraction of the muscles of the airways causing difficulty breathing)
• respiratory depression (reduction of respiratory activity).

Furthermore, the following side effects may occur for which there is not sufficient data
to establish the frequency:

• anemia (reduction of hemoglobin in the blood, a substance that carries oxygen in the blood)
• thrombocytopenia (reduction in the number of platelets in the blood)
• leukopenia/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
• headache
• myoclonus (rapid involuntary muscle twitch)
• paresthesia (tingling)
• syncope (transient loss of consciousness)
• tremor
• sedation
• confusional state
• drug abuse
• drug dependence
• withdrawal syndrome, following abrupt discontinuation of treatment
• withdrawal syndrome in newborns born to mothers chronically exposed to codeine during pregnancy
• hallucination
• euphoria (excitement)
• dysphoria (depressed mood with irritability and nervousness)
• hypotension (low blood pressure)
• acute renal failure (reduction of kidney function)
• interstitial nephritis (inflammation of the kidneys)
• hematuria (blood in the urine)
• anuria (cessation or reduction of urine production by the kidney)
• urinary retention (inability of the bladder to empty completely)
• diarrhea
• abdominal pain
• nausea
• vomiting
• constipation
• reactions to the stomach and intestines
• pancreatitis (inflammation of the pancreas)
• dyspnea (difficulty breathing)
• increased liver enzymes
• alteration of the INR (value used to express the time it takes for blood to coagulate)
• rhabdomyolysis (severe muscle damage)
• asthenia (weakness)
• malaise
• miosis (constriction of the pupils)
• edema (swelling due to fluid accumulation).

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform
your doctor or pharmacist. You can also report side effects directly through the website
www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Co-Efferalgan

Keep this medicine out of the sight and reach of children.
Keep the medicine in its original packaging to protect it from moisture.
Do not use this medicine after the expiry date which is reported on the blister and on the box after
EXP. The expiry date refers to the last day of that month.
Do not dispose of any medicine in 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 Co-Efferalgan Contains

• The active ingredients are: paracetamol and codeine phosphate. Each tablet contains 500 mg of paracetamol and 30 mg of codeine phosphate.
• The other ingredients are: sodiumhydrogen carbonate, anhydrous sodiumcarbonate, sodium benzoate (E211), sodium docusate, anhydrous citric acid, sorbitol (E420), povidone, aspartame (E951), natural grapefruit flavour (contains fructose, glucose, sucrose, ethyl alcoholand sulphites).

Description of the appearance of Co-Efferalgan and package contents
Co-Efferalgan is presented as effervescent tablets, white, flat and with a
break line.
It is available in packs of 16 tablets.

Marketing Authorisation Holder
UPSA S.A.S.
Rueil Malmaison - France

represented in Italy by
UPSA ITALY S.R.L.
Viale Luca Gaurico 9/11 – Rome

Manufacturer
UPSA S.A.S.
Avenue du Docteur Jean Bru, 304 - Agen - France
UPSA S.A.S.
Avenue des Pyrénées, 979 - Le Passage - France

Co-Efferalgan 500 mg + 30 mg film-coated tablets
paracetamol + codeine phosphate

Read this leaflet carefully before using 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 pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What is Co-Efferalgan and what it is used for
• 2. What you need to know before you use Co-Efferalgan
• 3. How to use Co-Efferalgan in adolescents
• 4. Possible side effects
• 5. How to store Co-Efferalgan
• 6. Package Contents and Other Information

1. What is Co-Efferalgan and what is it used for

Co-Efferalgan contains two active ingredients (paracetamol and codeine), which work in different ways.
Paracetamol works by relieving pain (analgesic) and reducing fever (antipyretic).
Codeine belongs to a group of drugs called opioid analgesics that relieve pain.
Co-Efferalgan is indicated in patients over the age of 12 yearsfor the treatment of symptoms of
moderate acute pain, which does not respond to treatment with other pain relievers such as
paracetamol or ibuprofen used alone.
See your doctor if you do not feel better or if you feel worse.

2. What you need to know before using Co-Efferalgan

Do not use Co-Efferalgan
If:

• you are allergic to paracetamol or propacetamol hydrochloride (a precursor of paracetamol), to codeine or to any of the other ingredients of this medicine (listed in section 6)
• you are less than 12 years old
• 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 removal of the tonsils or adenoids because you suffered from a breathing disorder called obstructive sleep apnea syndrome
• you have a liver enzyme that allows your body to transform codeine into a high amount of morphine (detected through urine testing) with a high probability of having serious side effects
• you are breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or pharmacist before using Co-Efferalgan.
Consult your doctor if:

• you suffer from mild/moderate reduced liver function (including Gilbert's syndrome, a condition characterized by excessive production of bilirubin, a substance that causes a yellowish discoloration of the skin and eyes)
• you suffer from severe liver problems
• you suffer from acute hepatitis (acute inflammation of the liver)
• you are taking medicines that stimulate liver enzymes (increasing the way the liver works)
• you suffer from glucose-6-phosphate dehydrogenase deficiency (a substance normally present in the human body, the deficiency of which can cause hemolytic anemia)
• you suffer from hemolytic anemia (a disease due to the destruction of some blood cells, red blood cells)
• you suffer from kidney failure (kidney diseases)
• you chronically abuse alcohol. Alcohol consumption during therapy is not recommended.
• you suffer from anorexia (an eating disorder characterized by a lack or reduction of appetite)
• you suffer from bulimia (an eating disorder in which a person ingests an excessive amount of food and then resorts to various methods to eliminate it in order not to gain weight)
• you suffer from cachexia (a condition characterized by extreme thinness, reduction of muscle mass and thinning of the skin due to chronic diseases)
• you suffer from chronic malnutrition
• you suffer from dehydration (severe loss of water/fluids from the body)
• you suffer from hypovolemia (reduced blood volume circulating in the body)
• you are in a condition of prolonged fasting
• you have a cough and produce phlegm
• you suffer from or have suffered from opioid, alcohol, prescription drug or illicit substance dependence
• you suffer from a mental disorder (e.g. major depression).

The habitual and prolonged use of codeine (one of the active ingredients of this medicine) can cause
dependence and misuse that can lead to overdose and even death. Do not
take this medicine for longer than necessary. Do not give this medicine to anyone else.
Paracetamol can cause severe skin reactions that can be fatal. The use of Co-Efferalgan
must be stopped at the first appearance of a skin rash or any other sign of
hypersensitivity (allergic reaction).
Opioid therapy can cause:

• respiratory depression (reduction of respiratory function) and sedation, lowering of the convulsive threshold (i.e. increased excitability of the nervous system, as in the case of 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 irritation of the abdomen)
• obstruction of the outflow of bile and pancreatic juice, as in the case of some diseases of the biliary tract, for example pancreatitis (inflammation of the pancreas) and cholelithiasis (presence of gallstones in the gallbladder)
• increased release of histamine, as in the case of asthma (bronchial obstruction)
• itching
• reduction of hormone levels
• inhibition of immunological function (i.e. the function of the body's defense system)
• muscle rigidity and myoclonus (rapid involuntary muscle twitch)
• urinary retention (difficulty emptying the bladder) particularly in patients with narrowing of the urethra (the last part of the urinary tract) or with enlargement of the prostate.

Use of high doses and/or for prolonged periods
The use of high doses or prolonged use of paracetamol can cause a liver disease
(hepatopathy) and alterations also serious to the kidney and blood.
Prolonged use of analgesics, including opioids, increases the risk of medication-overuse headache
(medication overuse headache). Furthermore, in elderly people, prolonged use can worsen a pre-existing condition.
Prolonged use of analgesics (for a period longer than 3 months) in patients with chronic headache
(headache), especially if repeated and frequent, can increase or worsen the headache. In these cases, it
is necessary to consult a doctor.
With prolonged use of opioids, a reduction in analgesic efficacy (tolerance) may occur.
Prolonged administration of codeine or at doses higher than therapeutic doses can cause
physical and psychological dependence (habituation) and withdrawal syndrome following sudden
discontinuation of administration, which can be observed in both patients and infants born to
codeine-dependent mothers. Co-Efferalgan should be used with caution in patients with dependence
or with a history of opioid dependence, and alternative analgesic therapies should be considered.

Elderly
Elderly patients may be at greater risk of side effects associated with the use of
opioids, such as respiratory depression and constipation.

Children and adolescents
Donot give codeine to relieve pain in children and adolescents after removal of the
tonsils or adenoids for obstructive sleep apnea syndrome.
Children and adolescents should be carefully 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 problems, as
the symptoms of morphine toxicity may be worse.

Other medicines and Co-Efferalgan
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.
In particular, tell your doctor if you are taking:

• other medicines that contain paracetamol, as if paracetamol is taken in high doses, serious side effects can occur
• othermedicines that contain opioids or other substances that depress the central nervous system, to avoid the risk of overdose or serious side effects
• coumarin anticoagulants including warfarin(medicines that delay blood clotting): the doctor will carry out more rigorous monitoring of INR values (time taken for the blood to clot)
• medicines or substances that stimulate liver enzymes (increasing the way the liver works), for example:
• rifampicin (an antibiotic)
• cimetidine (a medicine used in the treatment of stomach ulcers)
• antiepileptics (medicines used to treat epilepsy), such as glutethimide, phenobarbital, carbamazepine and phenytoin. If treated with phenytoin, do not take high doses or prolonged use of paracetamol.
• The use of these medicines with Co-Efferalgan requires extreme caution and must be carried out only under strict medical supervision.
• probenecid, a medicine used to treat hyperuricemia (high concentration of uric acid in the blood) and gout (inflammation of the joints due to uric acid deposition): the doctor will advise you to reduce the doses of Co-Efferalgan
• salicylamide(a pain reliever and fever reducer)
• flucloxacillin(an antibiotic): the doctor will monitor you more carefully to detect the possible onset of a condition that increases acids in the blood (metabolic acidosis)
• chloramphenicol(an antibiotic): may increase the risk of possible side effects
• medicines that slow down gastric emptying, such as anticholinergics: these medicines delay the effect of Co-Efferalgan.
• zidovudine(a medicine for the treatment of HIV)
• potent painkillers(buprenorphine, butorphanol, nalbuphine, nalorphine, pentazocine)
• nalmefene and naltrexone(medicines to treat dependence on alcohol and drugs, respectively)
• antihistamines(medicines to treat allergies)
• analgesics(alfentanil, destromoramide, dextropropoxyphene, fentanyl, dihydrocodeine, hydromorphone, morphine, oxycodone, pethidine, phenoperidine, remifentanil, sufentanil, tramadol)
• medicines to treat cough(dextromethorphan, noscapine, pholcodine, codeine, etymorphine)
• medicines to treat psychiatric disorders(chlorpromazine, haloperidol, levomepromazine, thioridazine)
• methadone(a medicine to treat drug dependence)
• meprobamate(a medicine to treat anxiety)
• benzodiazepines and barbiturates(medicines to treat insomnia and anxiety)
• medicinesto treatdepression(paroxetine, fluoxetine, bupropion, sertraline, imipramine, clomipramine, amitriptyline, nortriptyline, doxepin, mirtazapine, mianserine, trimipramine and monoamine oxidase inhibitors)
• antihypertensives(medicines to treat high blood pressure)
• baclofen, a medicine to reduce and relieve muscle spasms (excessive tension in muscles that occurs in various diseases)
• thalidomide, a medicine to treat multiple myeloma (a disease of the immune system, the body's defense system)
• celecoxib(a medicine that relieves inflammation)
• quinidine(a medicine to treat irregular heartbeat)
• dexamethasone(a medicine to treat various disorders such as inflammation and allergies)
• anticholinergics(medicines to treat various pathologies such as bladder problems, allergies and depression).

The concomitant use of Co-Efferalgan and sedatives such as benzodiazepines or related medicines
increases the risk of drowsiness, difficulty breathing (respiratory depression), coma and can
endanger the patient's life. For these reasons, concomitant use should be considered
only when alternative treatments cannot be used. If the doctor prescribes Co-Efferalgan together with sedatives, the dose and duration of concomitant treatment
must be established by your doctor. Tell your doctor about all the sedatives you are taking and carefully follow the doctor's recommendations on dosage. It
may be helpful to inform friends or family members to be aware of the onset of the above symptoms.
Contact your doctor when these symptoms occur.

Interference with blood tests
If the person taking the medicine needs to undergo blood tests, keep in mind that the administration of
paracetamol may interfere with the determination of uricemia (the amount of uric acid in the
blood) and glycemia (the amount of sugar in the blood).

Co-Efferalgan and alcohol
The concomitant use of alcohol and codeine may increase the sedative effect: drinking alcohol during
treatment with Co-Efferalgan is not recommended.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning a pregnancy, ask your doctor
or pharmacist for advice before taking this medicine.

Pregnancy
Paracetamol
Clinical experience with the use of paracetamol during pregnancy is limited.
Codeine
Available data are not sufficient to exclude an association between malformations and codeine use
during pregnancy.
Maternal use of codeine at any stage of pregnancy may be associated with scheduled cesarean delivery.
Use in the third trimester may be associated with an increased risk of urgent cesarean delivery, postpartum hemorrhage and the possible onset of opioid withdrawal symptoms in the newborn, including restlessness, excessive crying, tremors, increased muscle tone (hypertonia), increased respiratory rate (tachypnea), fever (pyrexia), vomiting and
diarrhea.

Breastfeeding
Co-Efferalgan is contraindicated during breastfeeding.

Driving and using machines
Co-Efferalgan can affect the ability to drive vehicles or use machines as it may
cause side effects such as drowsiness and cognitive impairment, such as impaired attention.

Co-Efferalgan coated tablets contain sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. it is essentially
"sodium-free".

3. How to use Co-Efferalgan

Use this medicine following exactly the instructions of your doctor or pharmacist. If you have
doubts, consult your doctor or pharmacist.
To avoid the risk of overdose, check that other medicines you are taking (with or without a prescription
medical prescription) do not contain paracetamol or codeine.
Accidental intake of an excessive dose of paracetamol can cause serious liver damage
and death (see section If you use more Co-Efferalgan than you should).

Adults and adolescents aged 12 years and over and weighing more than 60 kg
The recommended dose is 1 or 2 tablets, depending on the intensity of the pain, to be taken 1 to 3
times a day at intervals of at least 6 hours.

Adolescents aged 12 years and over and weighing less than 60 kg
The dosage must be determined based on 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.

Children under 12 years of age

Donot give Co-Efferalgan to children under 12 years of age.

Patients with kidney disease
If you suffer from a severe kidney disease, the interval between two administrations must be at least 8
hours.

Patients with liver disease
If you suffer from impaired liver function, the dose must be reduced or the interval between two
administrations prolonged.
The maximum dose should not exceed 4 tablets per day in case of:
adult patients weighing less than 50 kg, hepatopathy, Gilbert's syndrome, chronic alcoholism,
chronic malnutrition or dehydration.

Elderly
The initial dose should be halved compared to the recommended dosage for adults and may be,
subsequently, increased based on tolerability.

Duration of treatment
The medicine should not be taken for more than 3 days in a row. If the pain does not improve after 3
days, consult your doctor.

Method of administration
Oral use.
Swallow the film-coated tablet whole with a glass of water. Do not break or chew.

If you use more Co-Efferalgan than you should
In case of ingestion/accidental intake of an excessive dose of Co-Efferalgan, immediately warn
your doctor or go to the nearest hospital.

Paracetamol
Taking an excessive dose of paracetamol increases the risk of poisoning and can lead
to death, especially if:

• you suffer from liver disease
• you abuse alcohol
• you suffer from chronic malnutrition
• you are taking medicines or substances that stimulate liver enzymes (increasing the way the liver works). In case of taking very high doses of paracetamol, the symptoms that may occur within the first 24 hours include:
• nausea
• vomiting
• anorexia (loss or reduction of appetite)
• pallor
• malaise
• diaphoresis (profuse sweating).

The following have been observed after paracetamol overdose:

• sudden inability of the kidneys to function properly (acute renal failure),
• a condition in which small blood clots form in the bloodstream, blocking the smallest blood vessels (disseminated intravascular coagulation),
• rare cases of acute pancreatitis, an inflammation of the pancreas.

In case of ingestion of 7.5 g or more of paracetamol in adults and 140 mg per kg of body weight
in children, serious liver damage may occur with consequent alteration of the results of
some blood tests (AST, ALT, lactic dehydrogenase, bilirubin, prothrombin), coma (deep
state of unconsciousness) or death.
The symptoms of liver damage reach their peak after 3-4 days.

Codeine
The maximum dose of opioids varies from individual to individual.
Taking an excessive dose of codeine or other opioids can primarily lead to:

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

Treatment
The doctor, based on the nature and severity of the symptoms, will carry out the appropriate supportive therapy.

If you forget to use Co-Efferalgan
Do not take/give the adolescent a double dose to make up for a missed dose.

If you stop treatment with Co-Efferalgan
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience the following side effects STOPtreatment with this medicine and
contact your doctor immediately:

• skin reactions that may manifest with:
• itching,
• urticaria (appearance of wheals on the skin accompanied by itching)
• skin rash
• erythema (redness of the skin)
• erythema multiforme (condition characterized by the appearance of red spots on the skin with a "bull's-eye" appearance associated with itching)
• purpura (appearance of skin patches of various sizes, purple in color)
• Stevens Johnson syndrome (severe skin disease with the appearance of rashes and exfoliations)
• toxic epidermal necrolysis (severe skin disease characterized by redness, blistering lesions with areas of detachment and skin death)
• acute generalized exanthematous pustulosis (eruption of hundreds of superficial pustules spread all over the body)
• drug fixed eruption (eruption on the skin of red/purple color)
• allergic reactions that may manifest with:
• laryngeal edema (swelling of the throat)
• angioedema (swelling of hands, feet, ankles, face, lips, tongue and/or throat)
• anaphylactic reaction (severe allergic reaction), including hypotension (lowering of blood pressure)
• anaphylactic shock (severe allergic reaction)
• hypersensitivity
• bronchospasm (excessive and prolonged contraction of the muscles of the airways causing difficulty breathing)
• respiratory depression (reduction of respiratory activity)

Furthermore, the following side effects may occur for which there is not sufficient data to establish the frequency:

• anemia (reduction of hemoglobin in the blood, a substance that carries oxygen in the blood)
• thrombocytopenia (reduction in the number of platelets in the blood)
• leukopenia/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
• headache
• myoclonus (rapid involuntary muscle twitch)
• paresthesia (tingling)
• syncope (temporary loss of consciousness)
• tremor
• sedation
• confusional state
• drug abuse
• drug dependence
• withdrawal syndrome, following sudden discontinuation of treatment
• withdrawal syndrome in newborns born to mothers chronically exposed to codeine during pregnancy
• hallucination
• euphoria (excitement)
• dysphoria (depressed mood with irritability and nervousness)
• hypotension (lowering of blood pressure)
• acute renal failure (reduction of kidney function)
• interstitial nephritis (inflammation of the kidneys)
• hematuria (blood in the urine)
• anuria (cessation or reduction of urine production by the kidney)
• urinary retention (inability of the bladder to empty completely)
• diarrhea
• abdominal pain
• nausea
• vomiting
• constipation
• reactions to the stomach and intestines
• pancreatitis (inflammation of the pancreas)
• dyspnea (difficulty breathing)
• increased liver enzymes
• alteration of INR (value used to express the time it takes for blood to coagulate)
• rhabdomyolysis (severe muscle damage)
• asthenia (weakness)
• malaise
• miosis (constriction of the pupils)
• edema (swelling due to fluid accumulation).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the website
www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Co-Efferalgan

Keep this medicine out of the sight and reach of children.
This medicine does not require any particular storage conditions.
Do not use this medicine after the expiry date which is reported on the blister and on the package after
EXP. The expiry date refers to the last day of that month.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Co-Efferalgan contains

• The active ingredients are: paracetamol and codeine phosphate. Each tablet contains 500 mg of paracetamol and 30 mg of codeine phosphate.
• The other ingredients are
• core: povidone, microcrystalline cellulose, sodium croscarmellose and magnesium stearate
• coating: hypromellose (E464), titanium dioxide (E171) and propylene glycol (E1520).

Description of the appearance of Co-Efferalgan and contents of the pack
Co-Efferalgan is presented as white, film-coated, biconvex and oblong tablets.
It is available in packs of 16 tablets.

Marketing Authorisation Holder
UPSA S.A.S.
Rueil Malmaison - France

represented in Italy by
UPSA ITALY S.R.L.
Viale Luca Gaurico 9/11 – Rome

Manufacturer
UPSA S.A.S.
Avenue du Docteur Jean Bru, 304 - Agen - France
UPSA S.A.S.
Avenue des Pyrénées, 979 - Le Passage - France