Etopirina Extra

Leaflet attached to the packaging: patient information

Etopiryna Extra

250 mg + 200 mg + 50 mg tablets

Acetylsalicylic acid + Paracetamol + Caffeine

It is necessary to carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

This medicine should always be used in accordance with the description in this patient leaflet or as directed by a doctor or pharmacist.

• The leaflet should be kept in case it needs to be read again.
• If advice or additional information is needed, a pharmacist should be consulted.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.
• If there is no improvement after 3 days or if the patient feels worse, they should contact their doctor.

Table of contents of the leaflet

• 1. What is Etopiryna Extra and what is it used for
• 2. Important information before using Etopiryna Extra
• 3. How to use Etopiryna Extra
• 4. Possible side effects
• 5. How to store Etopiryna Extra
• 6. Package contents and other information

1. What is Etopiryna Extra and what is it used for

Etopiryna Extra is a combination medicine that combines the analgesic, anti-inflammatory, and antipyretic effects of acetylsalicylic acid and paracetamol. Caffeine enhances the analgesic effect of acetylsalicylic acid and paracetamol.

The medicine is recommended for use in the following indications:

headaches, particularly migraines, and other moderate pain, especially of inflammatory origin.

2. Important information before using Etopiryna Extra

When not to use Etopiryna Extra

• If the patient is allergic to acetylsalicylic acid, paracetamol, caffeine, or any of the other ingredients of this medicine (listed in section 6). Hypersensitivity to acetylsalicylic acid occurs in 0.3% of the population, including 20% of patients with asthma or chronic urticaria. Symptoms of hypersensitivity: urticaria, and even anaphylaxis can occur within 3 hours of taking acetylsalicylic acid.
• If the patient is allergic (hypersensitive) to other nonsteroidal anti-inflammatory drugs, with symptoms such as: bronchospasm, rhinitis, urticaria, anaphylaxis.
• If the patient has asthma, chronic respiratory diseases, hay fever, or nasal mucosal edema, as patients with these diseases may react to nonsteroidal anti-inflammatory drugs with asthma attacks, limited skin and mucosal edema (angioedema), or urticaria more frequently than other patients.
• If the patient has active gastric or duodenal ulcer disease and/or gastrointestinal bleeding (may cause gastrointestinal bleeding or exacerbation of ulcer disease).
• If the patient has severe liver, kidney, or heart failure.
• If the patient has cardiac arrhythmias.
• If the patient suffers from insomnia.
• If the patient has bleeding disorders (e.g., hemophilia, thrombocytopenia) and is being treated with anticoagulant medications (e.g., coumarin derivatives, heparin).
• If the patient has a deficiency of glucose-6-phosphate dehydrogenase (a rare hereditary disease).
• If the patient is taking methotrexate in doses of 15 mg per week or higher, due to the harmful effect on the bone marrow.
• In children and adolescents under 16 years of age, especially during viral infections, due to the risk of Reye's syndrome, a rare but serious disease that causes liver and brain damage.
• During pregnancy and breastfeeding.

Warnings and precautions

Before starting to use Etopiryna Extra, the patient should discuss it with their doctor or pharmacist.

Particular caution should be exercised when using Etopiryna Extra:

• if the patient is taking other medicines containing paracetamol, acetylsalicylic acid, and caffeine;
• in patients with non-specific colitis, bleeding disorders, asthma, or allergic disease in their medical history - they should consult their doctor before starting treatment.
• if the patient is taking oral antidiabetic drugs from the sulfonylurea group, due to the risk of enhancing the hypoglycemic effect (reducing blood glucose levels), and if the patient is taking medications for gout;
• if the patient has a history of hypoprothrombinemia, vitamin K deficiency, thrombocytopenia, or has been treated with anticoagulant medications;
• if the patient has juvenile rheumatoid arthritis and/or systemic lupus erythematosus and liver failure, as the toxicity of salicylates increases;
• if the patient has menstrual bleeding or is using an intrauterine contraceptive device;
• in patients with intracranial bleeding;
• if the patient has hypertension or heart failure;
• if the patient is taking methotrexate in doses less than 15 mg per week, due to the increased toxic effect of methotrexate on the bone marrow. Concomitant use with methotrexate in doses higher than 15 mg per week is contraindicated;
• before scheduled surgery. Due to the risk of prolonged bleeding time, both during and after surgery, the medicine should be discontinued 5 to 7 days before the scheduled surgery;
• in patients with hypertension and/or heart failure, as the use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with fluid retention and edema;
• if the patient is psychomotor agitated.

During the use of Etopiryna Extra, the patient should immediately inform their doctor if they experience severe diseases, including severe kidney disorders or sepsis (when bacteria and their toxins are present in the blood, leading to organ damage) or malnutrition, chronic alcoholism, or if they are also taking flucloxacillin (an antibiotic). In these situations, patients have been reported to develop a severe disease called metabolic acidosis (a blood and body fluid disorder), when they took paracetamol in regular doses for a longer period or when they took paracetamol with flucloxacillin. Symptoms of metabolic acidosis may include: severe breathing difficulties, including rapid deep breathing, drowsiness, nausea (nausea) and vomiting.

The patient should avoid concomitant use of Etopiryna Extra with NSAIDs (nonsteroidal anti-inflammatory drugs), including cyclooxygenase inhibitors.

Acetylsalicylic acid may cause an asthma attack in hypersensitive patients.

Very rarely, after taking nonsteroidal anti-inflammatory drugs (NSAIDs), severe skin reactions have been reported, which can be fatal, such as Stevens-Johnson syndrome (see section 4).

Treatment should be discontinued after the appearance of the first skin changes, such as rash, mucosal lesions, or any other symptoms of hypersensitivity.

Concomitant, long-term use of paracetamol and acetylsalicylic acid in high doses increases the risk of developing analgesic nephropathy.

Effect on laboratory tests. The use of paracetamol may be the cause of unreliable test results for uric acid (phosphotungstic acid method) and blood sugar (oxidase-peroxidase method).

Use in patients with liver and/or kidney function disorders

In patients with liver and/or kidney function disorders, there is a risk of increasing the adverse effects of the medicine, so it may be necessary to adjust the dose depending on the severity of liver and/or kidney failure.

The medicine is contraindicated in cases of severe liver and/or kidney failure.

Use in elderly patients

In elderly patients (over 65 years), the medicine should be used in smaller doses and at longer intervals, due to the increased risk of adverse effects in this patient group.

Etopiryna Extra and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.

Caution should be exercised when using Etopiryna Extra with:

• angiotensin-converting enzyme (ACE) inhibitors, as the medicine may reduce the antihypertensive effect of ACE inhibitors;
• acetazolamide, as acetylsalicylic acid may significantly increase the concentration and toxicity of acetazolamide;
• anticoagulant medications (e.g., heparin, warfarin), as the medicine may enhance the anticoagulant effect, increasing the risk of bleeding;
• antiepileptic drugs, as acetylsalicylic acid may enhance the toxic effect of valproic acid, while valproic acid may enhance the anti-aggregatory effect of acetylsalicylic acid;
• diuretics, as the medicine may reduce the effectiveness of diuretics and increase the ototoxicity of furosemide. Probenecid may affect the pharmacokinetics of paracetamol;
• methotrexate, as acetylsalicylic acid may enhance the toxic effect of methotrexate on the bone marrow. Concomitant use with methotrexate in doses of 15 mg per week or higher is contraindicated;
• nonsteroidal anti-inflammatory drugs (NSAIDs), as concomitant use of salicylates and other NSAIDs is not recommended due to the increased risk of adverse effects on the gastrointestinal tract;
• systemic glucocorticoids, as, except for hydrocortisone as replacement therapy in Addison's disease, when administered concomitantly with salicylates, they increase the risk of gastric ulcer and gastrointestinal bleeding, and reduce the serum salicylate concentration during treatment, while after its completion, they increase the risk of salicylate overdose;
• antidiabetic medications, as the medicine may enhance the hypoglycemic effect of antidiabetic medications. The medicine should not be used concomitantly with sulfonylurea derivatives;
• medicines that increase uric acid excretion (e.g., probenecid, sulfinpyrazone), as salicylates reduce the effect of medicines that increase uric acid excretion. The medicine should not be used concomitantly with medications for gout;
• digoxin, as the medicine may enhance its effect;
• thrombolytic medications, as concomitant administration of acetylsalicylic acid and thrombolytic medications, such as streptokinase and alteplase, may increase the risk of complications in elderly patients after a stroke;
• alcohol, as it often increases the frequency and severity of gastrointestinal bleeding. During treatment, alcohol should not be consumed;
• flucloxacillin (an antibiotic), due to the serious risk of blood and body fluid disorders (called metabolic acidosis), which must be treated urgently (see section 2);
• sedative or antiepileptic medications, such as phenobarbital, phenytoin, carbamazepine, and rifampicin, as concomitant use of paracetamol with these medications may lead to liver damage, even when paracetamol is used in recommended doses;
• metoclopramide and domperidone, as they increase the absorption and toxicity of paracetamol. Concomitant use should be avoided;
• cholestyramine, as it reduces the absorption of paracetamol;
• chloramphenicol, as paracetamol increases the serum concentration and toxicity of chloramphenicol;
• medicines that modify gastric emptying, as they may affect the absorption of paracetamol when used concomitantly;
• zidovudine, as concomitant administration of paracetamol with zidovudine may cause neutropenia and hepatotoxicity;
• oral contraceptives, cimetidine, and disulfiram, as they slow down the metabolism and/or excretion of caffeine;
• barbiturates, as they accelerate the metabolism of caffeine;
• analeptics and ergotamine, as the medicine may enhance the effect of other analeptics and ergotamine;
• adrenergic receptor agonists, as concomitant use with caffeine may cause tachycardia, additional central nervous system stimulation, and other toxic effects;
• mexiletine, ciprofloxacin, enoxacin, as they may reduce the elimination of caffeine and enhance its adverse effects;
• theophylline, as caffeine may increase the serum concentration of theophylline;
• monoamine oxidase inhibitors (MAOIs), as high doses of caffeine may enhance the adverse effects of MAOIs.

Using Etopiryna Extra with food, drink, and alcohol

During the use of the medicine, the patient should not consume alcohol, due to the increased risk of gastrointestinal mucosal damage.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, or thinks they may be pregnant or plans to have a child, they should consult their doctor or pharmacist before using this medicine.

Pregnancy

The medicine is contraindicated during pregnancy.

If the patient continues or starts treatment with Etopiryna Extra during pregnancy in accordance with their doctor's recommendations, they should use the medicine as recommended by their doctor and not take a higher dose than recommended.

Pregnancy - third trimester

Acetylsalicylic acid should not be used in a dose higher than 100 mg per day during the last 3 months of pregnancy, as it may harm the unborn baby or cause complications during delivery. The use of Etopiryna Extra may cause kidney and heart disorders in the unborn baby. This may affect the patient's and their baby's tendency to bleed and cause delayed or prolonged labor.

If the patient takes acetylsalicylic acid in small doses (up to 100 mg per day), close obstetric monitoring is necessary, as recommended by their doctor.

Pregnancy - first and second trimester

Due to the content of acetylsalicylic acid, the medicine should not be taken during the first 6 months of pregnancy, unless it is absolutely necessary and recommended by a doctor. If the patient needs treatment during this period or when trying to conceive, the smallest effective dose of the medicine should be used for the shortest possible time. Taking acetylsalicylic acid for a period longer than a few days, starting from the 20th week of pregnancy, may cause kidney disorders in the unborn baby, leading to low levels of amniotic fluid surrounding the baby (oligohydramnios) or narrowing of the arterial duct (ductus arteriosus) in the baby's heart. If longer treatment is necessary, the doctor may recommend additional monitoring.

Breastfeeding

The medicine is contraindicated during breastfeeding.

Fertility

This medicine belongs to the group of nonsteroidal anti-inflammatory drugs, which may have a negative effect on female fertility. This effect is transient and disappears after the end of treatment.

Driving and using machines

There is no data on the effect of the medicine on psychophysical abilities.

Etopiryna Extra contains hydrogenated castor oil

The medicine may cause indigestion and diarrhea.

3. How to use Etopiryna Extra

This medicine should always be used exactly as described in this patient leaflet or as directed by a doctor or pharmacist. In case of doubts, the patient should consult their doctor or pharmacist.

The medicine should be taken orally, with plenty of water. The medicine is recommended to be taken after a meal.

Usually, the recommended dose for adults and adolescents over 16 years of age is 1 to 2 tablets 3 times a day. The patient should use the smallest effective dose of the medicine. The dose should not exceed 6 tablets (1.5 g of acetylsalicylic acid, 1.2 g of paracetamol, and 0.3 g of caffeine) per day.

The medicine is intended for short-term use, and without consulting a doctor, the patient should not use the medicine for more than 3 days.

If the symptoms persist or worsen, or if new symptoms appear, the patient should contact their doctor.

Using a higher than recommended dose of Etopiryna Extra

In case of taking a higher dose than recommended, the patient should immediately contact their doctor or pharmacist.

Symptoms of acetylsalicylic acid overdose:

The first symptoms of acetylsalicylic acid poisoning are nausea, vomiting, tinnitus, and rapid breathing.

Other symptoms have also been observed, such as: hearing loss, vision disturbances, headaches, psychomotor agitation, drowsiness, and coma, seizures, hyperthermia (elevated body temperature).

In severe poisonings, serious acid-base and water-electrolyte disorders (metabolic acidosis and dehydration) occur.

Mild or moderate toxic symptoms occur after taking acetylsalicylic acid in a dose of 150-300 mg/kg body weight. Severe symptoms of poisoning occur after a dose of 300-500 mg/kg body weight.

A potentially fatal dose of acetylsalicylic acid is higher than 500 mg/kg body weight.

Death due to acetylsalicylic acid poisoning has been observed after taking a single dose of 10-30 g by adults. A case has also been reported of a patient who survived after taking 130 g of acetylsalicylic acid.

Treatment of overdose:

There is no specific antidote for acetylsalicylic acid.

In case of acetylsalicylic acid poisoning, the patient should:

• Induce vomiting and rinse the stomach (to reduce the absorption of the medicine). This procedure is effective within 3-4 hours after taking the medicine, and in case of poisoning with a very large dose of the medicine, even up to 10 hours.
• Administer activated charcoal in the form of a water suspension (in a dose of 50-100 g in adults and 30-60 g in children) to reduce the absorption of acetylsalicylic acid.
• In case of hyperthermia, the body temperature should be lowered by maintaining a low environmental temperature and using cool compresses.
• Any water-electrolyte disorders should be closely monitored and quickly corrected.
• To accelerate the excretion of acetylsalicylic acid by the kidneys and to treat acidosis, sodium bicarbonate should be administered intravenously. The urine pH should be maintained between 7.0 and 7.5.
• In very severe poisonings, when it is not possible to correct acid-base disorders with conservative treatment, and in cases of concomitant kidney failure, hemodialysis or peritoneal dialysis should be used. Dialysis effectively removes acetylsalicylic acid from the body and helps to correct acid-base and water-electrolyte disorders.
• In cases of prolonged prothrombin time, vitamin K should be administered.
• Medicines that depress the central nervous system, such as barbiturates, should not be used due to the risk of respiratory acidosis and coma.
• Patients with respiratory disorders should be provided with fresh air, and oxygen should be administered if necessary. If necessary, tracheal intubation and assisted ventilation should be performed.
• In case of shock, standard anti-shock treatment should be used.

Symptoms of paracetamol overdose:

In case of overdose, there is a risk of liver damage, so immediate hospitalization and administration of an antidote are necessary.

If the patient has taken a higher dose than they should, symptoms may appear within 24 hours and may include: nausea, vomiting, loss of appetite, pallor, and stomach pain. In case of overdose, the patient should immediately go to the nearest hospital, even if no symptoms are present.

Symptoms of caffeine overdose:

In case of caffeine overdose, insomnia, fatigue, muscle tremors, hallucinations, tachycardia, extrasystoles, seizures are observed. There is no specific antidote. In case of overdose, symptomatic treatment should be used.

Missing a dose of Etopiryna Extra

If a dose is missed, the patient should take the next dose at the scheduled time. The patient should not take a double dose to make up for the missed dose.

If the patient has any further doubts about using the medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Blood and lymphatic system disorders

Thrombocytopenia, anemia due to microbleeding from the gastrointestinal tract, hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency, leukopenia, agranulocytosis, eosinopenia, methemoglobinemia, thrombocytosis, increased risk of bleeding, prolonged bleeding time, prolonged prothrombin time.

Immune system disorders

Hypersensitivity reactions: itching, rash, urticaria, erythema, Stevens-Johnson syndrome, angioedema, bronchospasm, anaphylaxis.

Hypersensitivity to acetylsalicylic acid occurs in 0.3% of the population, in 4% of patients with asthma, and in 20% of patients with chronic urticaria. Symptoms of hypersensitivity (such as urticaria, and even anaphylaxis) may occur within 3 hours of taking the medicine.

Metabolism and nutrition disorders

A serious disease that can cause blood acidification (metabolic acidosis), in patients with severe disease taking paracetamol (see section 2) - frequency not known (frequency cannot be estimated from available data).

Nervous system disorders

Headache, insomnia.

Eye disorders

Vision disturbances.

Ear and labyrinth disorders

Tinnitus, hearing disturbances, vertigo, reversible hearing loss.

Tinnitus and ringing in the ears are the first symptoms of salicylate poisoning.

Cardiac and vascular disorders

Due to the treatment with NSAIDs, reports of edema, hypertension, and heart failure have been made.

Respiratory, thoracic, and mediastinal disorders

Pulmonary edema of non-cardiac origin (mainly in chronic or acute poisoning). Bronchospasm in patients hypersensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Gastrointestinal disorders

Indigestion, heartburn, feeling of fullness or burning in the upper abdomen, nausea, vomiting, diarrhea, loss of appetite, stomach pain, gastrointestinal bleeding, gastric mucosal damage, exacerbation of ulcer disease, perforations, pancreatitis.

Gastric ulcer occurs in 15% of patients taking acetylsalicylic acid for a long time.

Hepatobiliary disorders

Focal liver cell necrosis, liver tenderness and enlargement, especially in patients with juvenile rheumatoid arthritis, systemic lupus erythematosus, rheumatic fever, or liver disease in their medical history, transient increase in serum aminotransferase activity, alkaline phosphatase, and bilirubin concentration.

Skin and subcutaneous tissue disorders

Skin rashes of various types, itching, rarely blisters or purpura.

Very rare cases of severe skin reactions have been reported.

Renal and urinary disorders

Proteinuria, presence of leukocytes and erythrocytes in urine, nephropathy with renal papillary necrosis, interstitial nephritis.

In case of overdose: significant decrease in creatinine clearance or acute renal tubular necrosis with renal function disorders.

General disorders and administration site conditions

Fever.

Caffeine may cause dependence in susceptible individuals and may cause a withdrawal effect after the end of treatment.

Reporting side effects

If side effects occur, including any side effects not listed in this leaflet, the patient should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products

Al. Jerozolimskie 181C

02-222 Warsaw

Tel.: +48 22 49 21 301

Fax: +48 22 49 21 309

Website: https://smz.ezdrowie.gov.pl

Side effects can also be reported to the marketing authorization holder.

By reporting side effects, it is possible to gather more information on the safety of the medicine.

5. How to store Etopiryna Extra

The medicine should be stored in a place invisible and inaccessible to children.

Do not store above 30°C. Store in the original packaging.

Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month.

Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Package contents and other information

What Etopiryna Extra contains

• The active substances of the medicine are acetylsalicylic acid, paracetamol, and caffeine. Each tablet contains 250 mg of acetylsalicylic acid, 200 mg of paracetamol, and 50 mg of caffeine.
• The other ingredients are: corn starch; microcrystalline cellulose; hydrogenated castor oil; aluminum oxide, roasted.

What Etopiryna Extra looks like and contents of the pack

A cardboard box contains 10 or 20 elongated tablets, white to yellow in color, with a biconvex shape, placed in an aluminum/PVC blister pack.

Marketing authorization holder and manufacturer

Zakłady Farmaceutyczne POLPHARMA S.A.

ul. Pelplińska 19, 83-200 Starogard Gdański

tel. +48 22 364 61 01

Date of last revision of the leaflet: