Etopiryna extra

Package leaflet: Information for the patient

Etopiryna Extra
250 mg + 200 mg + 50 mg tablets
Acetylsalicylic acid + Paracetamol + Caffeine
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.
This medicine should always be used according to the instructions provided in this patient leaflet or as directed by a
physician or pharmacist.

• Keep this leaflet, as you may need to read it again.
• If you need advice or further information, consult your pharmacist.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.
• If there is no improvement after 3 days, or if your condition worsens, consult a doctor.

Table of contents

1. What Etopiryna Extra is and what it is used for
2. Important information before taking Etopiryna Extra
3. How to take Etopiryna Extra
4. Possible side effects
5. How to store Etopiryna Extra
6. Contents of the pack and other information

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

Etopiryna Extra is a combination medicine that provides the analgesic, anti-inflammatory, and antipyretic effects of acetylsalicylic acid and paracetamol. Caffeine enhances the analgesic effect of acetylsalicylic acid and paracetamol.
This medicine is recommended for the following indications:
headaches, particularly migraine headaches, and other moderate-intensity 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 bronchial asthma or chronic urticaria. Symptoms of hypersensitivity: urticaria, and even shock, may occur within 3 hours after taking acetylsalicylic acid.
• If the patient has an allergy (hypersensitivity) to other nonsteroidal anti-inflammatory drugs (NSAIDs), manifesting with symptoms such as bronchospasm, rhinitis, urticaria, or shock.
• If the patient has bronchial asthma, chronic respiratory diseases, hay fever, or nasal mucosal edema, as patients with these conditions may react to nonsteroidal anti-inflammatory drugs with asthma attacks, limited skin and mucosal swelling (angioedema), or urticaria more frequently than other patients.
• If the patient has active gastric and/or duodenal ulcer disease, or inflammatory conditions or bleeding from the gastrointestinal tract (which may lead to gastrointestinal bleeding or exacerbation of ulcer disease).
• If the patient has severe hepatic, renal, or cardiac insufficiency.
• If the patient has cardiac arrhythmia.
• If the patient suffers from insomnia.
• If the patient has blood coagulation disorders (e.g., hemophilia, thrombocytopenia), or is being treated concomitantly with anticoagulant agents (e.g., coumarin derivatives, heparin).
• If the patient has glucose-6-phosphate dehydrogenase deficiency (a rare inherited disorder).
• If the patient is concurrently receiving methotrexate at weekly doses of 15 mg or higher, due to its harmful effect on 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 causing liver and brain damage.
• During pregnancy and breastfeeding.

Warnings and precautions
Before starting treatment with Etopiryna Extra, consult your doctor or pharmacist.
Exercise particular caution when using Etopiryna Extra:

• if the patient is taking other medicines containing paracetamol, acetylsalicylic acid, and caffeine;
• in patients with inflammatory bowel disease, blood coagulation disorders, asthma, or a history of allergic disease – they should consult a doctor before starting treatment;
• if the patient is taking oral antidiabetic sulfonylurea derivatives, due to the risk of enhanced hypoglycemic (blood glucose-lowering) effect, or 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 drugs;
• if the patient has juvenile rheumatoid arthritis and/or systemic lupus erythematosus, or hepatic insufficiency, as this increases salicylate toxicity;
• if the patient experiences uterine bleeding, excessive menstrual bleeding, or uses an intrauterine contraceptive device;
• in patients with intracranial hemorrhage;
• if the patient has hypertension or heart failure;
• if the patient is taking methotrexate at doses less than 15 mg per week, due to increased risk of methotrexate toxicity to bone marrow. Concurrent use with methotrexate at doses greater than 15 mg per week is contraindicated;
• before planned surgical procedures. 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 fluid retention and edema have been observed with the use of nonsteroidal anti-inflammatory drugs (NSAIDs);
• if the patient is psychomotorically agitated.

During treatment with Etopiryna Extra, immediately inform a doctor if the patient develops severe conditions, including severe kidney dysfunction or sepsis (when bacteria and their toxins circulate in the blood, leading to organ damage), malnutrition, chronic alcoholism, or if the patient is also taking flucloxacillin (an antibiotic). In these situations, patients have been reported to develop a serious condition called metabolic acidosis (a disturbance in blood and body fluid balance) when taking paracetamol regularly over a long period or when taking paracetamol together with flucloxacillin. Symptoms of metabolic acidosis may include: severe breathing difficulties, including rapid deep breathing, drowsiness, nausea, and vomiting.
Avoid concomitant use of Etopiryna Extra with NSAIDs (nonsteroidal anti-inflammatory drugs), including drugs inhibiting cyclooxygenase.
Acetylsalicylic acid may trigger asthma attacks in hypersensitive patients.
Very rarely, severe skin reactions, which may be fatal, such as Stevens-Johnson syndrome (see section 4), have been reported after taking nonsteroidal anti-inflammatory drugs (NSAIDs).
Treatment should be discontinued at the first signs of skin changes such as rash, mucosal lesions, or any other symptoms of hypersensitivity.
Long-term, concomitant use of paracetamol and acetylsalicylic acid at high doses increases the risk of analgesic nephropathy.
Effect on laboratory tests. The use of paracetamol may lead to inaccurate results in tests measuring uric acid concentration (phosphotungstic acid method) and blood glucose levels (peroxidase-oxidase method).

Use in patients with impaired liver and/or kidney function
In patients with impaired liver and/or kidney function, there is an increased risk of adverse drug reactions; therefore, dose adjustment may be necessary depending on the severity of hepatic and/or renal insufficiency.
The medicine is contraindicated in cases of severe hepatic and/or renal insufficiency.

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

Etopiryna Extra and other medicines
Inform your doctor or pharmacist about all medicines currently used, recently used, or planned for use.
Exercise caution 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 its concentration and thus its toxicity;
• anticoagulant drugs (e.g., heparin, warfarin), as the medicine may enhance anticoagulant effects, thereby increasing the risk of bleeding;
• antiepileptic drugs, as acetylsalicylic acid enhances the toxic effect of valproic acid, while valproic acid enhances the antiplatelet effect of acetylsalicylic acid;
• diuretics, as the medicine may reduce the effectiveness of diuretics and enhance the ototoxicity of furosemide. Probenecid may affect the pharmacokinetics of paracetamol;
• methotrexate, as acetylsalicylic acid enhances the toxic effect of methotrexate on bone marrow. Concomitant use with methotrexate at 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 increased risk of gastrointestinal adverse effects;
• systemic glucocorticoids, as, with the exception of hydrocortisone used as replacement therapy in Addison's disease, their concomitant administration with salicylates increases the risk of peptic ulcer disease and gastrointestinal bleeding, reduces plasma salicylate concentrations during treatment, and increases the risk of salicylate overdose after treatment cessation;
• antidiabetic drugs, as the medicine may enhance the hypoglycemic effect of antidiabetic agents. The medicine should not be used concomitantly with sulfonylurea derivatives;
• uricosuric agents (e.g., probenecid, sulfinpyrazone), as salicylates reduce the effect of uricosuric drugs. The medicine should not be used concomitantly with gout medications;
• digoxin, as the medicine may enhance its effect;
• thrombolytic agents, as combined administration of acetylsalicylic acid and thrombolytic agents such as streptokinase and alteplase may increase the risk of complications in elderly patients after hemorrhagic stroke;
• alcohol, as it increases the frequency and severity of gastrointestinal bleeding. Alcohol should not be consumed during treatment;
• flucloxacillin (antibiotic), due to a serious risk of blood and body fluid disturbances (called metabolic acidosis), which require urgent treatment (see section 2);
• sedatives or antiepileptic drugs such as phenobarbital, phenytoin, carbamazepine, and rifampicin, as concomitant use of paracetamol with these drugs may lead to liver damage, even when paracetamol is used at recommended doses;
• metoclopramide and domperidone, as they increase the absorption and thus the toxicity of paracetamol. Concomitant use should be avoided;
• cholestyramine, as it reduces the absorption of paracetamol;
• chloramphenicol, as paracetamol increases chloramphenicol plasma concentration and its toxicity;
• drugs modifying gastric emptying, as their concomitant use with paracetamol may affect its absorption;
• zidovudine, as combined 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 caffeine metabolism;
• analeptics and ergotamine, as the medicine may enhance the effects of other analeptics and ergotamine;
• adrenergic receptor agonists, as their concomitant use with caffeine may cause tachycardia, additional central nervous system stimulation, and other toxic effects;
• mexiletine, ciprofloxacin, enoxacin, as they may reduce caffeine elimination and enhance its adverse effects;
• theophylline, as caffeine may increase theophylline plasma concentration;
• monoamine oxidase inhibitors (MAOIs), as high doses of caffeine may enhance the adverse effects of MAOIs.

Use of Etopiryna Extra with food, drink, and alcohol
Do not consume alcohol during treatment, due to increased risk of gastrointestinal mucosal damage.

Pregnancy, breastfeeding, and effects on fertility
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult a 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 as advised by a doctor, she should use Etopiryna Extra strictly according to medical advice and should not exceed the recommended dose.

Pregnancy – third trimester
Do not use acetylsalicylic acid in doses exceeding 100 mg per day during the last three months of pregnancy, as it may harm the unborn child or cause complications during delivery. Use of Etopiryna Extra may cause kidney and heart disorders in the unborn child. It may affect the tendency to bleeding in both the mother and the child and may delay or prolong labor.
If the patient takes acetylsalicylic acid at low doses (up to 100 mg per day), strict obstetric monitoring according to medical advice is required.

Pregnancy – first and second trimester
Due to the presence of acetylsalicylic acid, this medicine should not be used during the first six months of pregnancy unless absolutely necessary and prescribed by a doctor. If treatment is necessary during this period or when trying to conceive, the lowest effective dose for the shortest possible duration should be used. Use of acetylsalicylic acid for longer than a few days from week 20 of pregnancy may cause kidney dysfunction in the unborn child, leading to low levels of amniotic fluid (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the child's heart. If treatment longer than a few days is required, 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 adversely affect fertility in women. This effect is reversible and resolves after discontinuation of treatment.

Driving and operating machinery
There is no data available on the effect of the medicine on psychomotor performance.

Etopiryna Extra contains hydrogenated castor oil
The medicine may cause indigestion and diarrhea.

3. How to use Etopiryna Extra

This medicine should always be taken exactly as described in this patient leaflet or as directed by
your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.
The medicine should be taken orally, with plenty of water. It is recommended to take the medicine after a meal.
The usual dose for adults and adolescents over 16 years of age is 1 to 2 tablets three times
daily. The lowest effective dose should be used. Do not exceed a daily dose of
6 tablets (1.5 g acetylsalicylic acid, 1.2 g paracetamol, and 0.3 g caffeine).
This medicine is intended for short-term use only. Without consulting a doctor, the patient should not
use the medicine for longer than 3 days.
If symptoms persist or worsen, or if new symptoms occur, consult a doctor.
Taking more Etopiryna Extra than recommended
In case of overdose, seek immediate medical advice from a doctor or pharmacist.
Symptoms of acetylsalicylic acid overdose:
The first signs of acetylsalicylic acid poisoning include nausea, vomiting, tinnitus (ringing in the ears),
and rapid breathing.
Other observed symptoms include: hearing loss, visual disturbances, headache,
psychomotor agitation, drowsiness and coma, convulsions, and hyperthermia (elevated body temperature).
Severe poisonings may lead to serious acid-base and fluid-electrolyte imbalances (metabolic acidosis and dehydration).
Mild or moderately severe toxic symptoms occur after acetylsalicylic acid doses of 150–300 mg/kg body weight.
Severe poisoning symptoms occur after doses of 300–500 mg/kg body weight.
A potentially lethal dose of acetylsalicylic acid exceeds 500 mg/kg body weight.
Fatalities due to acetylsalicylic acid poisoning have been reported following single doses of 10 to 30 g in adults.
There has also been a reported case of survival after ingestion of 130 g of acetylsalicylic acid.
Treatment of overdose:
There is no specific antidote for acetylsalicylic acid.
In case of acetylsalicylic acid poisoning, the following measures should be taken:

• Induce vomiting and perform gastric lavage (to reduce drug absorption). This procedure is effective within 3–4 hours after ingestion, and in cases of very large overdoses, may be effective up to 0–10 hours.
• Administer activated charcoal as an aqueous suspension (50–100 g for adults, 30–60 g for children) to reduce absorption of acetylsalicylic acid.
• In case of hyperthermia, reduce body temperature by maintaining a cool environment and applying cold compresses.
• Carefully monitor fluid and electrolyte imbalances and correct them promptly.
• To enhance renal excretion of acetylsalicylic acid and treat acidosis, administer intravenous sodium bicarbonate. Maintain urine pH between 7.0 and 7.5.
• In very severe poisonings, when conservative treatment fails to correct acid-base imbalances or in cases of concomitant renal failure, hemodialysis or peritoneal dialysis should be performed. Dialysis effectively removes acetylsalicylic acid from the body and helps correct acid-base and fluid-electrolyte imbalances.
• In cases of prolonged prothrombin time, administer vitamin K.
• Do not use central nervous system depressants such as barbiturates, due to the risk of respiratory acidosis and coma.
• Patients with respiratory disturbances should be provided with fresh air and oxygen. If necessary, perform endotracheal intubation and initiate assisted ventilation.
• In case of shock, apply standard anti-shock measures.

Symptoms of paracetamol overdose:
Overdose carries a risk of liver damage; therefore, immediate hospitalization and administration of an antidote are required.
If a patient has taken more than the recommended dose, symptoms may appear within 24 hours and may
include: nausea, vomiting, anorexia, pallor, and abdominal pain. In case of overdose, the patient should
seek immediate medical attention at the nearest hospital, even if no symptoms are present.
Symptoms of caffeine overdose:
Caffeine overdose may cause insomnia, fatigue, muscle tremors, delirium, tachycardia, extrasystoles, and convulsions.
There is no specific antidote. In case of overdose, symptomatic treatment should be administered.
If you forget to take Etopiryna Extra
If a dose is missed, take the next dose at the scheduled time. Do not take a double dose to make up for
a missed dose.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Blood and lymphatic system disorders
Thrombocytopenia, anemia due to gastrointestinal microbleeding, hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency, leukopenia, agranulocytosis, eosinopenia, methemoglobinemia, thrombocytopenia, increased risk of bleeding, prolonged bleeding time, prolonged prothrombin time.

Immune system disorders
Hypersensitivity reactions: itching, rash, urticaria, erythema, Stevens-Johnson syndrome, angioedema, bronchospasm, anaphylactic shock.
Hypersensitivity to acetylsalicylic acid occurs in 0.3% of the population, in 4% of patients with bronchial asthma, and in 20% of patients with chronic urticaria. Symptoms of hypersensitivity (such as urticaria, and even shock) may occur within 3 hours after taking the medicine.

Metabolism and nutrition disorders
A serious condition that may cause acidification of the blood (so-called metabolic acidosis) in patients with severe illness taking paracetamol (see section 2) – frequency unknown (frequency cannot be estimated from available data).

Nervous system disorders
Headache, insomnia.

Eye disorders
Visual disturbances.

Ear and labyrinth disorders
Tinnitus, hearing disturbances, dizziness, reversible hearing loss.
Tinnitus and ringing in the ears are the first signs of salicylate poisoning.

Cardiac and vascular disorders
Edema, hypertension, and heart failure have been reported in association with NSAID therapy.

Respiratory, thoracic and mediastinal disorders
Non-cardiogenic pulmonary edema (occurring mainly in chronic or acute poisoning).
Bronchospasm in patients with hypersensitivity to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Gastrointestinal disorders
Dyspepsia, heartburn, feeling of fullness or burning in the epigastrium, nausea, vomiting, diarrhea, loss of appetite, abdominal pain, gastrointestinal bleeding, gastric mucosal damage, exacerbation of peptic ulcer disease, perforations, pancreatitis.
Gastric ulceration occurs in 15% of patients taking acetylsalicylic acid long-term.

Hepatobiliary disorders
Focal necrosis of liver cells, tenderness and enlargement of the liver, particularly in patients with juvenile rheumatoid arthritis, systemic lupus erythematosus, rheumatic fever, or history of liver disease; transient increases in serum aminotransferase activity, alkaline phosphatase, and bilirubin concentration.

Skin and subcutaneous tissue disorders
Various types of skin eruptions, 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 reduction in creatinine clearance or acute tubular necrosis with impaired kidney function.

General disorders and administration site conditions
Fever.
Caffeine may cause dependence in particularly susceptible individuals and may lead to withdrawal symptoms upon discontinuation of therapy.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions 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
Adverse effects may also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Etopiryna Extra

Keep this medicine out of sight and reach of 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 specified month.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the package and other information

What Etopiryna Extra contains

• The active substances 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: maize starch; microcrystalline cellulose; hydrogenated castor oil; aluminium oxide, calcined.

What Etopiryna Extra looks like and contents of the pack
The cardboard box contains 10 or 20 elongated tablets, white to yellow in colour, biconvex, placed in an Aluminium/PVC blister pack.
Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01