Co-efferalgan

Italy
Brand name Co-efferalgan
Form tablets, effervescent
Active substance / Dosage
PARACETAMOL
CODEINE PHOSPHATE
Prescription type Prescription only – non-repeatable
ATC code
N02AJ06
Registration number 027989
Manufacturer UPSA SAS
Co-efferalgan tablets, effervescent

Table of Contents

Package leaflet: Information for the user

Co-Efferalgan 500 mg + 30 mg film-coated tablets
paracetamol + codeine phosphate
Please read all of this leaflet carefully before you start using this medicine because 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 they have the same symptoms as yours, because it could be harmful.
  • If you experience any adverse reactions, including those not listed in this leaflet, contact 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 taking Co-Efferalgan
  3. How to take Co-Efferalgan in adolescents
  4. Possible side effects
  5. How to store Co-Efferalgan
  6. Contents of the pack and other information

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

Co-Efferalgan 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 relieve pain.
Co-Efferalgan is indicated in patients over 12 years of age for the treatment of symptoms of acute moderate pain that does not respond to 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 using Co-Efferalgan

Do not use Co-Efferalgan
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 insufficiency), as codeine may worsen your condition
  • you are between 0 and 18 years old and have recently undergone tonsil or adenoid removal due to a breathing disorder called obstructive sleep apnoea syndrome
  • you have a liver enzyme that causes your body to convert codeine into a high amount of morphine (detected through urine testing), increasing the likelihood of serious adverse effects
  • you are breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or pharmacist before using Co-Efferalgan.
During treatment with Co-Efferalgan, inform your doctor immediately if:

  • you have mild/moderate impairment of liver function (including Gilbert’s syndrome, a condition characterized by excessive production of bilirubin, a substance causing yellowish discoloration of the skin and eyes)
  • you suffer from severe liver problems
  • you have 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, whose deficiency may cause haemolytic anaemia)
  • you suffer from haemolytic anaemia (a disease caused by destruction of certain blood cells, red blood cells)
  • you suffer from renal failure (kidney disease)
  • you chronically consume alcohol. Alcohol consumption during therapy is not recommended.
  • you suffer from anorexia (an eating disorder characterized by lack or reduction of appetite)
  • you suffer from bulimia (an eating disorder in which a person ingests excessive amounts of food and then uses various methods to eliminate it to avoid weight gain)
  • you suffer from cachexia (a condition characterized by extreme thinness, reduced muscle mass, and thinning of the 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 hypovolemia (reduced volume of circulating blood)
  • you are in a prolonged fasting state
  • you have a cough with phlegm production
  • you suffer from or have previously suffered from dependence on opioids, alcohol, prescription medicines, or illicit substances
  • you suffer from a mental disorder (e.g. major depression)
  • you suffer from severe illnesses, including severe renal impairment or sepsis (when bacteria and their toxins circulate in the blood causing organ damage), malnutrition, chronic alcoholism, or if you are also taking flucloxacillin (an antibiotic). In patients with these conditions, a serious condition called metabolic acidosis (an abnormality in blood and body fluids) has been reported when paracetamol is used regularly for prolonged periods or when paracetamol is taken in combination with flucloxacillin. Symptoms of metabolic acidosis may include: severe breathing difficulties with deep rapid breathing, drowsiness, nausea, and vomiting.

The habitual and prolonged use of codeine (one of the active substances in this medicine) may cause
dependence and misuse, potentially leading to overdose and even death. Do not take this medicine longer than necessary. Do not give this medicine to anyone else.
Paracetamol may cause severe skin reactions that can be fatal. Treatment with Co-Efferalgan should be discontinued at the first sign of skin rash or any other sign of hypersensitivity (allergic reaction).
Opioid therapy may cause:

  • respiratory depression (reduced respiratory function) and sedation
  • lowering of the 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)
  • increased release of histamine, as in asthma (obstruction of the bronchi)
  • 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 stricture (narrowing of the final part of the urinary tract) or enlarged prostate.

Use of high doses and/or for prolonged periods
The use of high or prolonged doses of paracetamol may cause liver disease (hepatopathy) and serious alterations affecting the kidneys and blood.
Prolonged use of analgesics, including opioids, increases the risk of medication-overuse headache. Additionally, in elderly patients, prolonged use may worsen an existing condition.
Prolonged use of analgesics (for more than 3 months) in patients with chronic headache, especially if frequent and recurrent, may increase or worsen headache. In such cases, medical advice must be sought.
With prolonged use of opioids, reduced analgesic effectiveness (tolerance) may occur.
Prolonged administration of codeine or doses higher than therapeutic levels may lead to physical and psychological dependence (addiction) and withdrawal syndrome following abrupt discontinuation, which may occur both in patients and in newborns born to codeine-dependent mothers. Co-Efferalgan 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 higher 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 Co-Efferalgan
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Other medicines and paracetamol
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 in the treatment of stomach ulcers)
  • antiepileptic 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.
  • The use of these medicines with Co-Efferalgan requires extreme caution and must only be done under strict medical supervision.
    • probenecid, a medicine used to treat hyperuricaemia (elevated uric acid levels in the blood) and gout (joint inflammation due to uric acid deposits): your doctor may advise reducing the dose of Co-Efferalgan
    • salicylamide (an analgesic and antipyretic medicine)
    • flucloxacillin (an antibiotic): your doctor will monitor you more closely for possible development of a condition causing increased acid levels in the blood (called metabolic acidosis)
    • chloramphenicol (an antibiotic): may increase the risk of potential adverse effects
    • medicines that slow gastric emptying, such as anticholinergics: these medicines delay the effect of Co-Efferalgan
    • zidovudine (a medicine for the treatment of HIV)
    • potent analgesics (buprenorphine, butorphanol, nalbuphine, nalorphine, pentazocine)
    • nalmefene and naltrexone (medicines for treating dependence on alcohol and drugs, respectively)
    • 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, doxepin, 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 Co-Efferalgan and sedative medicines such as benzodiazepines or related substances increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. For these reasons, concomitant use should only be considered when alternative treatments are not possible.
If your doctor prescribes Co-Efferalgan together with sedative medicines, the dose and duration of concomitant treatment must be determined by your doctor. Inform your doctor about all sedative medicines you are taking and follow your doctor’s dosage recommendations carefully. It may be helpful to inform friends or relatives to watch for the onset of the symptoms listed above. Contact your doctor if such symptoms occur.
Interference with blood tests
If the person taking the medicine needs to undergo blood tests, note that paracetamol administration may interfere with the measurement of serum uric acid levels (uricaemia) and blood glucose levels (glycaemia).
Co-Efferalgan and alcohol
Concomitant use of alcohol and codeine may enhance the sedative effect: alcohol consumption during treatment with Co-Efferalgan is not recommended.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Paracetamol
Clinical experience with paracetamol use during pregnancy is limited.
Codeine
Available data are insufficient to exclude an association between malformations and codeine use during pregnancy.
Maternal use of codeine at any stage of pregnancy may be associated with elective caesarean delivery. Use during 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
Co-Efferalgan is contraindicated during breastfeeding.
Driving and use of machinery
Co-Efferalgan may affect your ability to drive or operate machinery, as it may cause adverse effects such as drowsiness and cognitive disturbances, including impaired attention.
Co-Efferalgan film-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 exactly as prescribed 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.
Accidentally taking an excessive dose of paracetamol may cause severe liver damage
and death (see section If you take more Co-Efferalgan than you should).
Adults and adolescents aged 12 years and older with body weight over 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 older with body weight under 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.
Children under 12 years of age
Do not give Co-Efferalgan 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 cases 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 half the recommended adult dose and may subsequently be increased 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.
Swallow the film-coated tablet whole with a glass of water. Do not break or chew.
If you take more Co-Efferalgan than you should
In case of accidental ingestion/overdose of Co-Efferalgan, 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 suffer from liver disease
  • you abuse alcohol
  • you suffer from chronic malnutrition
  • you are taking medicines or substances that stimulate liver enzymes (increasing liver activity).
    Following an overdose of paracetamol, symptoms that may appear within the first 24 hours include:
  • nausea
  • vomiting
  • anorexia (lack of appetite or reduced appetite)
  • pallor
  • malaise
  • diaphoresis (excessive sweating).

After paracetamol overdose, the following have been observed:

  • sudden inability of the kidneys to function properly (acute kidney injury),
  • 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.

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 (AST, ALT, lactate dehydrogenase, bilirubin, prothrombin), coma (deep unconsciousness), or death.
Symptoms of liver damage 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 may primarily cause:

  • respiratory depression, ranging from reduced 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 the symptoms.
If you forget to take Co-Efferalgan
Do not take/give the adolescent a double dose to make up for a missed dose.
If you stop using Co-Efferalgan
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 gets them.
If you experience the following side effects, STOP treatment with this medicine and contact your
doctor immediately:

  • skin reactions that may include:
    • itching,
    • urticaria (appearance of itchy, raised welts on the skin)
    • skin rash
    • erythema (redness of the skin)
    • erythema multiforme (a condition characterized by red, target-like skin lesions associated with itching)
    • purpura (appearance of purple-colored skin patches of varying sizes)
    • Stevens-Johnson syndrome (a serious skin illness with skin eruptions and peeling)
    • toxic epidermal necrolysis (a severe skin condition characterized by redness, blistering, and areas of skin detachment and death)
    • generalized pustular eruption (widespread eruption of hundreds of superficial pustules across the body)
    • drug-induced fixed eruption (a red/violet skin rash)
  • allergic reactions that may include:
    • 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 airway muscles causing breathing difficulties)
  • respiratory depression (reduced breathing activity)

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

  • anemia (reduction in hemoglobin in the blood, the substance that carries oxygen)
  • thrombocytopenia (reduced number of platelets in the blood)
  • leukopenia/agranulocytosis/neutropenia (reduced 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 (sudden, involuntary muscle jerks)
  • paresthesia (tingling)
  • syncope (transient loss of consciousness)
  • tremor
  • sedation
  • confusion
  • medication abuse
  • drug dependence
  • withdrawal syndrome following sudden discontinuation of treatment
  • withdrawal syndrome in newborns born to mothers who were chronically exposed to codeine during pregnancy
  • hallucination
  • euphoria (excitement)
  • dysphoria (depressed mood with irritability and restlessness)
  • hypotension (low blood pressure)
  • acute renal failure (reduced kidney function)
  • interstitial nephritis (inflammation of the kidneys)
  • hematuria (blood in the urine)
  • anuria (cessation or reduction in urine production by the kidneys)
  • urinary retention (inability of the bladder to empty completely)
  • diarrhea
  • abdominal pain
  • nausea
  • vomiting
  • constipation
  • gastrointestinal reactions
  • pancreatitis (inflammation of the pancreas)
  • dyspnea (difficulty breathing)
  • increased liver enzymes
  • changes in INR (a value used to express the time it takes for blood to clot)
  • rhabdomyolysis (serious muscle damage)
  • asthenia (weakness)
  • malaise
  • miosis (constriction of the pupils)
  • edema (swelling due to fluid accumulation).
  • a serious condition that may make the blood more acidic (called metabolic acidosis), in patients with a severe illness using paracetamol (see section 2), frequency not known (cannot be estimated from the available data).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via 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 special storage conditions.
Do not use this medicine after the expiry date stated on the blister and the outer carton after EXP. The expiry date refers to the last day of that month.
Do not dispose of medicines 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 Co-Efferalgan contains

  • The active substances are: paracetamol and codeine phosphate. Each tablet contains 500 mg of paracetamol and 30 mg of codeine phosphate.
  • The other components are:
    • core: povidone, microcrystalline cellulose, croscarmellose sodium 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, oblong tablets.
It is available in packs containing 16 tablets.
Marketing Authorization 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

Package leaflet: Information for the user

Co-Efferalgan 500 mg + 30 mg effervescent tablets
paracetamol + codeine phosphate
Please read all of this leaflet carefully before you start 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 may be harmful.
  • If you experience any adverse reactions, including those not listed in this leaflet, talk to 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 taking Co-Efferalgan
  3. How to take Co-Efferalgan
  4. Possible side effects
  5. How to store Co-Efferalgan
  6. Contents of the pack and other information

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

Co-Efferalgan 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 relieve pain.
Co-Efferalgan 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 should know before using Co-Efferalgan

Do not use Co-Efferalgan
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 insufficiency), as codeine may worsen your condition
  • you are between 0 and 18 years old and have undergone tonsil or adenoid removal due to a breathing disorder called obstructive sleep apnea 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
Talk to your doctor or pharmacist before using Co-Efferalgan.
During treatment with Co-Efferalgan, inform your doctor immediately 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 suffer from severe liver problems
  • you have 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; its deficiency may cause hemolytic anemia)
  • you suffer from hemolytic anemia (a disease caused by destruction of certain blood cells, red blood cells)
  • you suffer from renal insufficiency (kidney disease)
  • you chronically consume alcohol. Alcohol consumption during treatment is not recommended
  • you suffer from anorexia (an eating disorder characterized by lack or reduction of 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 hypovolemia (reduced volume of circulating blood)
  • you are in a state of prolonged fasting
  • you have a cough with mucus production
  • you suffer or have suffered from dependence on opioids, alcohol, prescription medicines, or illicit substances
  • you suffer from a mental disorder (e.g., major depression)
  • you suffer from serious illnesses, including severe renal impairment or sepsis (when bacteria and their toxins circulate in the blood causing organ damage), or from malnutrition, chronic alcoholism, or if you are also taking flucloxacillin (an antibiotic). In patients with these conditions, a serious condition called metabolic acidosis (an abnormality in blood and body fluids) has been reported when paracetamol is used regularly for prolonged periods or when paracetamol is taken concomitantly with flucloxacillin. Symptoms of metabolic acidosis may include: severe breathing difficulties with deep rapid breathing, drowsiness, nausea, and vomiting.

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

  • respiratory depression (reduced respiratory 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 diseases, e.g., pancreatitis (inflammation of the pancreas) and cholelithiasis (presence of gallstones in the gallbladder)
  • increased release of histamine, as in asthma (airway obstruction)
  • itching
  • reduced hormone levels
  • inhibition of immunological function (i.e., the body's defense system)
  • muscle rigidity and myoclonus (involuntary rapid muscle jerks)
  • urinary retention (difficulty emptying the bladder), particularly in patients with urethral stricture (narrowing of the urinary tract) or enlarged prostate.

Use of high doses and/or for prolonged periods
The use of high or prolonged doses of paracetamol may cause liver disease (hepatopathy) and serious
alterations in the kidney and blood.
Prolonged use of analgesics, including opioids, increases the risk of medication-overuse headache.
Moreover, in elderly patients, prolonged use may worsen a pre-existing condition.
Prolonged use of analgesics (for more than 3 months) in patients with chronic headache, especially if
repeated and frequent, may increase or worsen headache. In such cases, medical advice should be
sought.
With prolonged use of opioids, reduced analgesic efficacy (tolerance) may occur.
Prolonged administration of codeine or administration at doses higher than therapeutic may lead to
physical and psychological dependence (addiction) and withdrawal syndrome following sudden
cessation of treatment, which may be observed both in patients and in newborns born to codeine-
dependent mothers. Co-Efferalgan should be used with caution in patients with dependence or a
history of opioid dependence, and alternative analgesic therapies should be considered.
Elderly
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 apnea 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 problems, as symptoms of
morphine toxicity may be more severe.
Other medicines and Co-Efferalgan
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Other medicines and paracetamol
In particular, inform your doctor if you are taking:

  • other medicines containing paracetamol, since serious adverse effects may occur if paracetamol is taken at 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 stricter monitoring of INR values (time taken for blood to clot)
  • medicines or substances that stimulate liver enzymes (increasing liver activity), for example:
    • rifampicin (an antibiotic)
    • cimetidine (a medicine used in the treatment of stomach ulcer)
  • antiepileptics (medicines used to treat epilepsy), for example glutethimide, phenobarbital, carbamazepine, and phenytoin. In case of treatment with phenytoin, do not take high or prolonged doses of paracetamol.
  • The use of these medicines with Co-Efferalgan requires extreme caution and should only be done under strict medical supervision.
    • probenecid, a medicine used for the treatment of hyperuricemia (high concentration of uric acid in the blood) and gout (joint inflammation due to uric acid deposits): your doctor will advise you to reduce the dose of Co-Efferalgan
    • salicylamide (an analgesic and antipyretic medicine)
    • flucloxacillin (an antibiotic): your doctor will monitor you more closely for possible onset of a disorder increasing acid levels in the blood (called metabolic acidosis)
    • chloramphenicol (an antibiotic): may increase the risk of possible adverse effects
    • medicines that slow gastric emptying, such as anticholinergics: these medicines delay the effect of Co-Efferalgan
    • zidovudine (a medicine for the treatment of HIV)
    • potent analgesics (buprenorphine, butorphanol, nalbuphine, nalorphine, pentazocine)
    • nalmefene and naltrexone (medicines for treating dependence on alcohol and drugs, respectively)
    • antihistamines (medicines for treating allergies)
    • analgesics (alfentanil, dextromoramide, dextropropoxyphene, fentanyl, dihydrocodeine, hydromorphone, morphine, oxycodone, pethidine, phenoperidine, remifentanil, sufentanil, tramadol)
    • medicines for treating cough (dextromethorphan, noscapine, pholcodine, codeine, ethylmorphine)
    • 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)
    • 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 defense 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 Co-Efferalgan and sedative medicines such as benzodiazepines or related
medicines increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and
can be life-threatening. For these reasons, concomitant use should only be considered when
alternative treatments are not possible.
If your doctor prescribes Co-Efferalgan together with sedative medicines, the dose and duration of
concomitant treatment must be determined by your doctor. Inform your doctor about all sedative
medicines you are taking and follow your doctor's dosage recommendations carefully. It may be
helpful to inform friends or relatives to watch for the signs and symptoms listed above. Contact your
doctor if these symptoms occur.
Interference with blood tests
If the person taking the medicine needs to undergo blood tests, note that administration of
paracetamol may interfere with the measurement of uric acid levels (uricemia) and blood sugar levels
(glycemia).
Co-Efferalgan and alcohol
Concomitant use of alcohol and codeine may increase sedative effects: alcohol consumption during
treatment with Co-Efferalgan 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.
Pregnancy
Paracetamol
Clinical experience with the use of paracetamol during pregnancy is limited.
Codeine
Available data are insufficient to exclude an association between malformations and codeine use
during pregnancy.
Maternal use of codeine at any stage of pregnancy may be associated with planned cesarean section.
Use in the third trimester may be associated with an increased risk of emergency cesarean section,
postpartum hemorrhage, and 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 use of machines
Co-Efferalgan may affect your ability to drive or operate machinery because it may cause adverse
effects such as drowsiness and cognitive disturbances, including attention impairment.
Co-Efferalgan effervescent tablets contain sodium
This medicine contains 384.64 mg of sodium (the main component of table salt) per tablet. This
corresponds to approximately 19% of the maximum recommended daily dietary intake for an adult.
Talk to 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.
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 disorder causing accumulation of phenylalanine
because the body cannot properly eliminate it.
Co-Efferalgan effervescent tablets contain sorbitol (E420)
This medicine contains 300 mg of sorbitol per tablet, 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 been diagnosed with hereditary fructose intolerance, a rare genetic disorder in which patients
cannot properly metabolize fructose, consult 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, equivalent to 58.5 mg/3250 mg.
Co-Efferalgan effervescent tablets, grapefruit flavour, also contain 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 intolerance to certain sugars, consult your doctor before taking this medicine.
Co-Efferalgan effervescent tablets contain grapefruit flavour, which in turn contains sulphites
Rarely, it may cause severe hypersensitivity reactions and bronchospasm.
Co-Efferalgan effervescent tablets, grapefruit flavour, contain 0.5 mg of alcohol (ethanol) per tablet.
The amount per tablet corresponds to a small quantity of beer or wine (traces). The small amount of
alcohol in this medicine will not produce significant effects.

3. How to use Co-Efferalgan

Use 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 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 Co-Efferalgan than you should).

Adults and adolescents aged 12 years and older with body weight over 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 older with body weight under 60 kg
Dosage should be determined based on 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.

Children under 12 years of age
Do not give Co-Efferalgan 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 daily dose must not exceed 4 tablets in the following cases:
adult patients weighing less than 50 kg, hepatic impairment, Gilbert's syndrome, chronic alcoholism, chronic malnutrition, or dehydration.

Elderly
The initial dose should be half the recommended adult dose and may subsequently be increased according to tolerance.

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.
Allow the effervescent tablet to dissolve in a glass of water. Do not swallow or chew.

If you take more Co-Efferalgan than you should
In case of accidental ingestion/overdose of Co-Efferalgan, 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 induce liver enzymes (increasing liver activity).

Following ingestion of very high doses of paracetamol, symptoms appearing within the first 24 hours may include:

  • nausea
  • vomiting
  • anorexia (loss or reduced appetite)
  • pallor
  • malaise
  • diaphoresis (excessive sweating).

After paracetamol overdose, the following have been observed:

  • sudden inability of the kidneys to function properly (acute kidney injury),
  • 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.

Ingestion of 7.5 g or more of paracetamol in adults, or 140 mg per kg of body weight in children, may result in severe liver damage, leading to abnormal blood test results (AST, ALT, lactate dehydrogenase, bilirubin, prothrombin), coma (deep unconsciousness), or death.
Symptoms of liver damage 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 may primarily lead to:

  • respiratory depression, ranging from decreased respiratory rate to apnea (absence of breathing),
  • extreme sedation, ranging from stupor to coma,
  • miosis (pupil constriction).

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 Co-Efferalgan
Do not take/don’t give the adolescent a double dose to make up for a missed dose.

If you stop taking Co-Efferalgan
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 include:
    • itching
    • urticaria (appearance of itchy skin welts)
    • skin rash
    • erythema (redness of the skin)
    • erythema multiforme (appearance of red skin spots with a "target-like" appearance associated with itching)
    • purpura (appearance of purple-colored skin patches of varying sizes)
    • Stevens-Johnson syndrome (a serious skin disease with eruptions and skin peeling)
    • toxic epidermal necrolysis (a serious skin disease characterized by redness, blistering lesions, and areas of skin detachment and death)
    • generalized exanthematous pustulosis (eruption of hundreds of superficial pustules spread over the entire body)
    • fixed drug eruption (skin rash appearing as red/violet-colored lesions)
  • Allergic reactions that may include:
    • 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 airway muscles causing breathing difficulties)
  • Respiratory depression (reduced respiratory activity).

Additionally, the following side effects may occur, for which insufficient data are 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
  • Headache
  • Myoclonus (sudden, involuntary muscle twitch)
  • Paraesthesia (tingling sensations)
  • Syncope (transient loss of consciousness)
  • Tremor
  • Sedation
  • Confusional state
  • Medication abuse
  • Drug dependence
  • Withdrawal syndrome following abrupt discontinuation of treatment
  • Withdrawal syndrome in newborns born to mothers who were chronically exposed to codeine during pregnancy
  • Hallucination
  • Euphoria (excitement)
  • Dysphoria (depressed mood with irritability and nervousness)
  • Hypotension (low blood pressure)
  • 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
  • Changes in INR (a value used to express the time it takes for blood to clot)
  • Rhabdomyolysis (serious muscle damage)
  • Asthenia (weakness)
  • Malaise
  • Miosis (constriction of the pupils)
  • Oedema (swelling due to fluid accumulation).
  • A serious condition that may make the blood more acidic (called metabolic acidosis), in patients with a severe illness who are using paracetamol (see section 2), frequency unknown (cannot be estimated from the available data).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via 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.
Store the medicine in the original packaging to protect it from moisture.
Do not use this medicine after the expiry date stated on the strip and the carton after EXP. The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Co-Efferalgan contains

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

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

Marketing Authorization 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