Leaflet: information for the user

Cod-Efferalgan 500mg/ 30mg effervescent tablets

Paracetamol/codeine phosphate hemihydrate

Read this leaflet carefully before you start taking this medicine, because

it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Cod-Efferalgan is used in adults and adolescents who weigh 50 kg or more (approximately 15 years old or older) for the relief of moderate acute pain for which the use of ibuprofen or paracetamol as the sole analgesic is not considered appropriate.

Do not take Cod-Efferalgan:

• if you are allergic to the active ingredients or any of the other components (listed in section 6)
• in cases of severe liver failure or decompensated active liver failure
• if you have bronchial asthma
• if you have respiratory insufficiency
• children and adolescents under 15 years old
• to relieve pain in children and adolescents (0-18 years old) after tonsillectomy or adenoidectomy due to obstructive sleep apnea syndrome
• if you know you metabolize codeine very quickly to morphine
• if you are breastfeeding

Warnings and precautions

Consult your doctor or pharmacist before starting to take Cod-Efferalgan.

• The medication will be administered with caution to patients with renal or hepatic function disorders, anemia, or chronic cardiorespiratory insufficiency.
• Inform your doctor or pharmacist if you suffer or have suffered from opioid dependence, alcohol, prescription medications, or illicit substances, or if you suffer from mental disorders (e.g. major depression).
• As with all analgesics, it should not be administered for prolonged periods, except on medical advice.
• Paracetamol can cause severe skin reactions such as acute generalized pustular psoriasis (PEAG), Stevens-Johnson syndrome (SSJ), and toxic epidermal necrolysis (NET), which can be fatal. Discontinue use at the first appearance of skin rash or any other sign of hypersensitivity.
• The frequent use of analgesics over a long period can cause or worsen headaches. If you suffer from chronic headaches and have been taking analgesics for more than 3 months, at least on alternate days, do not increase the analgesic dose, but consult your doctor.

During treatment with Cod-Efferalgan, immediately inform your doctor if:

• You have severe diseases, such as severe renal failure or sepsis (when bacteria and their toxins circulate in the blood, causing damage to organs), or if you suffer from malnutrition, chronic alcoholism, or if you are also taking flucloxacillin (an antibiotic). A severe disease called metabolic acidosis (a blood and fluid anomaly) has been reported in patients in these situations when paracetamol is used at regular doses for a prolonged period or when paracetamol is taken with flucloxacillin. Symptoms of metabolic acidosis may include: severe respiratory distress with deep and rapid breathing, somnolence, feeling unwell (nausea) and vomiting.

Effects on the Central Nervous System

The depressant effects of opioids such as codeine on the Central Nervous System (CNS) can cause severe respiratory depression.

Prolonged use of this medication increases the risk of medication overuse headache.

Treatment with opioids, particularly chronic use, can induce an increase in pain in certain patients.

It is not recommended to consume alcohol during treatment with Cod-Efferalgan.

Effects on the Respiratory System

Opioids cause respiratory depression due to CNS depressant effects. The risk of respiratory depression may be increased by concomitant medication use and pharmacogenetic factors.

Cod-Efferalgan should be used with caution in patients with asthma.

Gastrointestinal Effects

The administration of opioids can mask symptoms of acute abdominal diseases.

Caution should be exercised in cases of biliary tract disease, such as pancreatitis and cholestasis.

Dermatological Effects

Pruritus.

Endocrine Effects

Decreased hormone levels, so use with caution in patients with hormonal disorders.

Musculoskeletal Effects

Muscle stiffness and myoclonus.

Urogenital Effects

Urinary retention. Use with caution in patients with urethral spasms or prostatic hypertrophy.

CARDIOVASCULAR AND CEREBROVASCULAR EFFECTS

Possible hemodynamic effects.

Tolerance

Prolonged use of opioids can produce a decrease in analgesic efficacy or tolerance.

- The prolonged and regular administration of codeine (one of the active ingredients of this medication) can produce physical and psychological dependence, addiction, or misuse. This can lead to overdose and/or death. Do not take this medication for longer than necessary. Do not give this medication to others.

- In order to avoid the risk of overdose, check that other medications you are taking (with or without a prescription) do not contain paracetamol.

- Administration of higher doses of paracetamol than recommended carries the risk of severe liver damage. Administer an antidote as soon as possible.

- Paracetamol should be used with caution in cases of mild or moderate liver insufficiency.

To avoid the risk of overdose or severe adverse effects, check that other medications you are taking (with or without a prescription) do not contain opioids or other CNS depressants.

CYP2D6 Metabolism

Codeine is metabolized by the liver enzyme CYP2D6 to morphine, its active metabolite. If you have a deficiency or are completely lacking this enzyme, you will not obtain adequate analgesic effect. However, if you are an ultra-rapid metabolizer, you may have a higher risk of developing opioid toxicity adverse effects even at commonly prescribed doses.

Alternative analgesic treatment is recommended for patients who are ultra-rapid metabolizers.

Low-codeine metabolizers:

Patients with low CYP2D6 metabolizer phenotype have a reduced ability to form morphine from codeine and therefore do not experience analgesic effect with codeine treatment, but may experience adverse effects.

Children and Adolescents

In pediatric patients, carefully monitor signs of progression of CNS depression associated with codeine, such as excessive somnolence and reduced respiratory rate.

Children with compromised respiratory function

Codeine is not recommended for use in children in whom respiratory function may be compromised, including neuromuscular, cardiac, or respiratory disorders, upper airway abnormalities, or pulmonary infections, multiple trauma, or extensive surgical procedures.

Post-operative use in children

There are reports of post-operative codeine administration to children after tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome that led to rare but life-threatening adverse events, including death.

Use in elderly patients

Geriatric patients may have an increased risk of experiencing adverse effects associated with opioids, such as respiratory depression and constipation. A lower initial dose than usual is recommended for elderly patients.

These patients also have a high probability of using concomitant medications, which can increase the risk of medication interactions.

Other medications and Cod-Efferalgan

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

In particular, if you are using the following medication, it may be necessary to modify the dose or discontinue treatment:

• Flucloxacillin (antibiotic): due to a severe risk of blood and fluid disorder (denominated metabolic acidosis with high anion gap) that must be treated urgently (see section 2).

Effect of other medications on Cod-Efferalgan

-Associated with paracetamol:

1. May increase the toxicity of chloramphenicol.
2. If you take phenytoin concomitantly, it may produce a decrease in paracetamol effectiveness and an increase in the risk of hepatotoxicity.
3. Consider reducing the paracetamol dose when administered concomitantly with probenecid.
4. Salicylamide may prolong the elimination half-life (t1/2) of paracetamol.
5. Be cautious when administering paracetamol concomitantly with enzyme-inducing substances, such as barbiturates, isoniazid, carbamazepine, rifampicin, and ethanol.

-Associated with codeine:

The concomitant use of codeine with other opioid medications such as alfentanil, dextromoramide, dextropropoxyphene, dihydrocodeine, fentanyl, hydromorphone, morphine, oxycodone, pethidine, pethidine, phenoperidine, remifentanil, sufentanil, tramadol, methadone, and cough suppressants, such as dextromethorphan, noscapine, codeine, and etilmorphine, may intensify CNS depressant effects, including sedation and respiratory depression, increasing the risk of fatal overdose.

The concomitant use of agonist/antagonist opioids and partial agonist opioids (buprenorphine, butorphanol, nalbuphine, nalorphine, pentazocine) may produce a reduction in analgesic effect and opioid withdrawal symptoms.

Other CNS depressants, such as barbiturates; anxiolytics and antidepressants, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), benzodiazepines, and hypnotics may potentiate the CNS depressant effects of codeine.

Other medications that may cause drowsiness, such as analgesics, cough suppressants, and substitution treatments, neuroléptics, barbiturates, benzodiazepines, anxiolytics, and other benzodiazepines (meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), antihistamines H1 sedatives, central-acting antihypertensive medications, baclofen, and talidomide, may have an additional sedative effect with codeine.

Other medications that are metabolized by or inhibit CYP2D6such as SSRIs (paroxetine, fluoxetine, bupropion, and sertraline), neuroléptics (chlorpromazine, haloperidol, levomepromazine, thioridazine), and tricyclic antidepressants (imipramine, clomipramine, amitriptyline, nortriptyline), celecoxib, quinidine, dexamethasone, and rifampin may reduce the analgesic effect of codeine.

Concomitant administration of anticholinergics with opioids, including codeine, may potentiate intestinal inhibition and increase the risk of intestinal paralysis.

Naltrexone, as an opioid antagonist, blocks the analgesic effect of codeine.

Effect of Cod-Efferalgan on other medications

Be cautious with the concomitant use of paracetamol and anticoagulants such as warfarin.

Taking Cod-Efferalgan with food and drinks

Consuming alcohol may potentiate the toxic effect of paracetamol, so do not take alcoholic beverages during treatment. Concomitant use of alcohol and codeine may potentiate CNS depression.

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

This medication is not recommended during pregnancy and lactation, as paracetamol is excreted in breast milk in small amounts. There have been reports of pruritus in newborns. If used, it should always be under medical prescription, evaluating the possible risks and benefits of treatment. Do not exceed the recommended dose.

At therapeutic doses, codeine and its active metabolite may be present in breast milk at very low doses and are unlikely to affect the lactating infant. However, if the patient is an ultra-rapid metabolizer of CYP2D6, higher levels of the active metabolite, morphine, may be found in breast milk, and in rare cases, this may cause opioid toxicity symptoms in the infant, which can be fatal.

Driving and operating machinery

This medicationmay cause drowsiness, altering mental and/or physical ability. If you experience these effects, avoid driving vehicles or operating machinery.

If you feel drowsy, dizzy, or have visual disturbances while taking this medication, do not drive or operate machinery until you have checked that your ability to perform these activities is not affected.

Alcohol may potentiate this effect, so do not take alcoholic beverages during treatment.

Cod-Efferalgan contains aspartame (E-951), sodium, sorbitol (E-420), sodium benzoate, glucose, fructose, sucrose, ethanol, and sulfites

This medication contains 30 mg of aspartame in each effervescent tablet.

Aspartame contains a source of phenylalanine that may be harmful in cases of phenylketonuria (PKU), a rare genetic disorder in which phenylalanine accumulates because the body is unable to eliminate it correctly.

This medication contains 300 mg of sorbitol in each effervescent tablet.

Sorbitol is a source of fructose. If your doctor has told you that you (or your child) have an intolerance to certain sugars, or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which the patient is unable to break down fructose, consult your doctor before taking this medication.

This medication contains 385 mg of sodium (main component of table salt/for cooking) in each effervescent tablet. This is approximately 19.25% of the recommended daily maximum sodium intake for an adult.

This medication contains 59 mg of sodium benzoate in each effervescent tablet.

This medication contains glucose and sucrose. If your doctor has told you that you have an intolerance to certain sugars, consult your doctor before taking this medication.

This medication contains 5 mg of fructose in each effervescent tablet.

This medication contains 0.5 mg of alcohol (ethanol) in each effervescent tablet. The amount per effervescent tablet of this medication is equivalent to a small amount of beer or wine. The small amount of alcohol contained in this medication has no perceptible effect.

This medication contains sorbitol, which may rarely cause severe hypersensitivity reactions and bronchospasm.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

This medication is administered orally.

Dissolve 1 or 2 tablets in a glass of water and ingest the contents after the effervescence has ceased.

The groove should not be used to break the tablet.

This medication should not be taken for more than 3 days. If the pain does not improve after 3 days, seek advice from your doctor.

Adults

The recommended dose is 1 or 2 effervescent tablets dissolved in a glass of water, up to 4 times a day, as needed, in intervals of no less than 6 hours. The maximum daily dose of codeine should not exceed 240 mg.

The administration of the medication is subject to the appearance of painful and feverish symptoms, and the dosage can be reduced as the symptoms disappear.

Use in children and adolescents

This medication is not recommended for use in children and adolescents under 15 years old. Children under 12 years old should not take Cod-Efferalgan due to the risk of severe respiratory problems.

Adolescents weighing 50 kg or more (and over 15 years old):The recommended dose is 1 to 2 effervescent tablets every 6 hours, as needed, up to a maximum codeine dose of 240 mg per day (8 tablets). This dose is calculated based on weight (0.5 to 1 mg/kg).

Older adults

Older adults should reduce the dose as they are more sensitive to the effects and adverse reactions of this medication.

Renal insufficiency

In case of moderate or severe kidney disease, the maximum dose per administration is 1 tablet. Depending on the severity of your disease, your doctor will tell you if you should take the medication with a minimum interval of 6 or 8 hours.

Liver disease

Take the amount of medication prescribed by your doctor with a minimum interval of 8 hours between each dose.

Do not take more than 4 tablets (2 grams of paracetamol) in 24 hours, divided into several doses.

If you take more Cod-Efferalgan than you should

The symptoms of overdose that typically appear within the first 24 hours include nausea, vomiting, loss of appetite, pallor, discomfort, and diaphoresis.

A paracetamol overdose is considered to be the ingestion of a single dose of more than 6 g in adults and more than 100 mg per kg of body weight in children.

In case of overdose or accidental ingestion, consult the Toxicology Information Service. Phone (91) 562 04 20.

Patients undergoing barbiturate therapy or chronic alcoholics may be more susceptible to the toxicity of a paracetamol overdose.

The treatment consists of aspiration and gastric lavage, administration of activated charcoal orally, and alkalization of the urine, preferably with sodium bicarbonate, and normalization of potassium levels. To control respiration, naxolone and N-acetylcysteine should be administered intravenously at adequate doses. In extreme cases, hemodialysis may be necessary.

The period in which treatment offers the greatest guarantee of effectiveness is within the 12 hours following ingestion of the overdose.

If you forget to take Cod-Efferalgan

Do not take a double dose to compensate for the missed doses.

Take the missed dose as soon as you remember and if your next dose is due soon, omit the missed dose and continue taking the medication at the usual time. In case of doubt, consult your doctor or pharmacist.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Associated with paracetamol at an unknown frequency:

- Blood and lymphatic system disorders: Thrombocytopenia, leucopenia, neutropenia

- Gastrointestinal disorders: Diarrhea, abdominal pain

- Hepatobiliary disorders: Increased liver enzymes

- Immune system disorders: Anaphylactic reaction (including hypotension), anaphylactic shock, hypersensitivity, angioedema

- Skin and subcutaneous tissue disorders: Urticaria, erythema, rash, purpura, pustulosis

Generalized acute exanthematous pustulosis, toxic epidermal necrolysis, Stevens-Johnson syndrome

• A serious condition that can make the blood more acidic (known as metabolic acidosis) in patients with severe disease who use paracetamol (see section 2).

Associated with codeine at an unknown frequency:

- Blood and lymphatic system disorders: Thrombocytopenia

- Ear and labyrinth disorders: Vertigo

- Gastrointestinal disorders: Abdominal pain, constipation, diarrhea, nausea, pancreatitis, vomiting

- General disorders and administration site conditions: Fatigue, malaise, edema

- Hepatobiliary disorders: Biliary colic, hepatitis

- Immune system disorders: Anaphylactic reaction, hypersensitivity

- Laboratory investigations: Increased alanine aminotransferase, increased aspartate aminotransferase, increased alkaline phosphatase in blood, increased amylase in blood, increased gamma-glutamyltransferase, Increased INR

- Musculoskeletal and connective tissue disorders: Rhabdomyolysis

- Nervous system disorders: Dizziness, myoclonus, paresthesia, somnolence, syncope, tremor

- Psychiatric disorders: Confusional state, addiction, abuse, dependence in cases of prolonged administration, withdrawal syndrome after sudden discontinuation of treatment and in newborns of mothers intoxicated with codeine during pregnancy, hallucinations

- Renal and urinary disorders: Renal failure, urinary retention

- Respiratory, thoracic and mediastinal disorders: Dyspnea, respiratory depression

- Skin and subcutaneous tissue disorders: Angioedema, erythema, pruritus, rash, urticaria

- Vascular disorders: Hypotension

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use: www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

No special storage conditions are required.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. Ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Cod-Efferalgan

• The active principles are paracetamol and codeine phosphate hemihydrate.

Each effervescent tablet contains 500 mg of paracetamol and 30 mg of codeine phosphate hemihydrate.

• The other components are aspartame, sodium hydrogen carbonate, anhydrous sodium carbonate, anhydrous citric acid, sorbitol, sodium docusate, sodium benzoate, povidone, and lemon aroma.

Appearance of Cod-Efferalganand contents of the packaging

White, round, scored tablets, packaged in aluminum strips, presented in containers holding 20 effervescent tablets.

Marketing Authorization Holder

UPSA SAS

3 rue Joseph Monier

92500 Rueil-Malmaison

France

Responsible for Manufacturing

UPSA

979, Avenue des Pyrénées

47520 - Le Passage

France

O

UPSA

304, avenue du Dr Jean Bru

47000 - Agen

France

Local Representative

NEWLINE PHARMA, S.L.U.

Calle Tarragona 151-157, Planta 11, Puerta 1, Bloque A

08014 Barcelona (Spain)

Tel.: 931851380

Date of the last review of this leaflet: January 2025

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/