Agrypin

Package leaflet: Information for the user

Agrypin
325 mg + 30 mg + 10 mg,
film-coated tablets
Paracetamolum + Pseudoephedrini hydrochloridum + Dextromethorphani hydrobromidum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.
This medicine should always be taken exactly as described in this patient leaflet or as directed by
your doctor or pharmacist.

• Keep this leaflet so that you can read it again if needed.
• If you need advice or further information, please consult your pharmacist.
• If you experience any adverse reactions, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.
• If there is no improvement or if you feel worse after 3 days, you should contact your doctor.

Contents of the leaflet

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

1. What Agrypin is and what it is used for

Agrypin contains three active substances: paracetamol, pseudoephedrine hydrochloride, and dextromethorphan hydrobromide. It has analgesic, antipyretic, decongestant (reducing nasal mucosal congestion and swelling), and antitussive effects. Agrypin is a medicine intended for the treatment of adults and children over 6 years of age and adolescents. Agrypin is indicated for the short-term symptomatic relief of cold, influenza, influenza-like conditions, and acute sinusitis (fever, nasal congestion, cough, headache, sore throat, muscle and joint pain).

2. Important information before using Agrypin

When not to use Agrypin:

• if the patient is allergic to the active substances or to any of the other ingredients of this medicine (listed in section 6);
• if the patient is currently taking other medicines containing paracetamol;
• if the patient is taking MAO inhibitor drugs (medicines used, among others, in depression), as well as within 2 weeks after discontinuation of such treatment;
• if the patient has congenital glucose-6-phosphate dehydrogenase deficiency;
• if the patient has severe liver failure;
• if the patient has severe acute or chronic kidney disease or renal failure;
• if the patient has very high blood pressure (severe hypertension) or uncontrolled hypertension despite medication;
• if the patient has ischemic heart disease;
• if the patient has alcoholic liver disease;
• if the patient has bronchial asthma. Do not use during pregnancy and breastfeeding. Do not use in children under 6 years of age.

Warnings and precautions
Before starting treatment with Agrypin, consult a doctor or pharmacist.
Pseudoephedrine – one of the active substances in Agrypin – may be subject to abuse, and high doses of pseudoephedrine may be toxic. Continuous use may lead to taking higher doses of Agrypin than the recommended dose to achieve the desired effect, increasing the risk of overdose. Do not exceed the recommended maximum dose or the recommended duration of treatment (see section 3).
Treatment with this medicine may lead to dependence. Therefore, treatment should be short-term.
WARNING! The medicine contains paracetamol. Do not take simultaneously with other medicines containing paracetamol.
In case of overdose, contact a doctor immediately, even if no symptoms are present, as this may lead to life-threatening liver damage.
Do not take Agrypin with medicines containing dextromethorphan, pseudoephedrine, or other sympathomimetics (such as medicines used to treat bronchospasm, e.g. in asthma, nasal decongestants, appetite suppressants, or psychostimulants with amphetamine-like effects).

• Use in patients with liver impairment, alcohol abusers, or fasting patients increases the risk of liver damage.
• Use with caution in patients with hypertension, cardiac arrhythmias, pulmonary emphysema, increased intraocular pressure, benign prostatic hyperplasia, hyperthyroidism, diabetes, or in patients taking anxiolytics or tricyclic antidepressants.
• Do not use Agrypin in patients with renal failure or in cases of chronic cough with sputum production. Do not use in patients with respiratory insufficiency, bronchial asthma, or in patients at risk of respiratory failure.
• Use with caution in patients taking anticoagulant medicines.
• Consult a doctor even if the above warnings refer to conditions that occurred in the past.

Before taking Agrypin, talk to a doctor or pharmacist:

• If the patient is taking certain antidepressants or antipsychotics, Agrypin may interact with them, causing changes in mental status (e.g. agitation, hallucinations, coma) and other symptoms such as body temperature above 38°C, increased heart rate, unstable blood pressure, exaggerated reflexes, muscle rigidity, lack of coordination, and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea).

During treatment with Agrypin, sudden abdominal pain or rectal bleeding may occur due to inflammation of the large intestine (ischemic colitis). If such gastrointestinal symptoms occur, discontinue Agrypin and seek immediate medical advice. See section 4.
During treatment with Agrypin, reduced blood flow in the optic nerve may occur. In case of sudden vision loss, discontinue Agrypin and seek immediate medical help. See section 4.
During treatment with Agrypin, immediately inform the doctor if the patient has 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 such cases, patients taking paracetamol regularly for a prolonged period or taking paracetamol with flucloxacillin have been reported to develop a serious condition called metabolic acidosis (abnormality in blood and body fluids). Symptoms of metabolic acidosis may include severe breathing difficulties, including rapid deep breathing, drowsiness, nausea, vomiting.
Cases of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) have been reported after using medicines containing pseudoephedrine. PRES and RCVS are rare conditions that may involve reduced blood flow to the brain.
If symptoms suggestive of PRES or RCVS occur, immediately discontinue Agrypin and seek immediate medical help (symptoms, see section 4 "Possible side effects").

Agrypin and other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines planned for use.
Interactions with Agrypin result from the effects of its active ingredients:

Paracetamol

• Do not take simultaneously with other medicines containing paracetamol.
• Medicines that accelerate gastric emptying (e.g. metoclopramide) increase the absorption rate of paracetamol, whereas medicines that delay gastric emptying (e.g. propantheline) may delay paracetamol absorption.
• Concurrent use of paracetamol with MAO inhibitors (used, among others, in depression treatment) and within 2 weeks after stopping such treatment may cause agitation and fever.
• Concurrent use of paracetamol with zidovudine (AZT, used in HIV infection) may enhance the bone marrow toxicity of zidovudine.
• Paracetamol may enhance the effect of anticoagulant medicines (coumarin derivatives).
• Concurrent use of paracetamol with drugs that increase hepatic metabolism, such as certain sedatives or antiepileptic drugs (e.g. phenobarbital, phenytoin, carbamazepine), as well as rifampicin (used, among others, in tuberculosis treatment), may lead to liver damage, even when recommended doses of paracetamol are used.
• Concomitant administration with chloramphenicol (a broad-spectrum antibacterial antibiotic) may increase chloramphenicol plasma concentration.
• Inform your doctor or pharmacist if the patient is taking:
• flucloxacillin (antibiotic) due to serious risk of blood and body fluid disorders (called metabolic acidosis), which require urgent treatment (see section 2).

Pseudoephedrine

• Do not take with other sympathomimetics (see "Warnings and precautions" above), as this may increase blood pressure.
• Concurrent use with albuterol (used, among others, in asthma treatment) may enhance vasoconstrictive effects.
• Do not take concurrently with amitriptyline (used, among others, in depression).
• Ammonium chloride prolongs the duration of action of pseudoephedrine.
• Antacids (used to relieve heartburn and indigestion) may increase the absorption of pseudoephedrine.
• MAO inhibitors (used in depression treatment) reduce the elimination of pseudoephedrine from the body and increase its bioavailability.
• Do not take concurrently with furazolidone (an antibacterial medicine).
• Pseudoephedrine reduces the effect of antihypertensive medicines and may modify the effects of cardiac glycosides (used in heart failure).

Dextromethorphan

• Concurrent use with MAO inhibitors (medicines used in depression treatment) is contraindicated (see When not to use Agrypin).

Agrypin with food, drink and alcohol
Do not drink alcohol while taking this medicine. Alcohol consumption during paracetamol treatment may lead to hepatocyte necrosis and, consequently, liver failure.

Pregnancy and breastfeeding
During pregnancy and breastfeeding, or if pregnancy is suspected or planned, consult a doctor or pharmacist before using this medicine.
Use of Agrypin during pregnancy and breastfeeding is contraindicated.

Driving and operating machinery
Agrypin may affect the ability to drive and operate machinery. Exercise caution while taking this medicine.

Agrypin contains 3.9 mg of monohydrate lactose per 1 coated tablet
This medicine contains monohydrate lactose. If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking this medicine.

3. How to use Agrypin

This medicine should always be taken exactly as described in the patient information leaflet or as directed by a doctor or pharmacist. If in doubt, consult a doctor or pharmacist.
Agrypin should be taken orally.
Adults and adolescents over 12 years of age: 1 to 2 tablets, 3-4 times daily. Do not exceed 8 tablets per day.
Children aged 6 to 12 years: 1 tablet 3-4 times daily. Do not exceed 4 tablets per day.
If symptoms worsen or do not improve after 3 days, consult a doctor.

Overdose of Agrypin
In case of taking more than the recommended dose of Agrypin, seek immediate medical advice from a doctor or pharmacist. The medicine contains three active substances. Symptoms of overdose may result from the effect of one or all of the active substances.
If a patient takes more than the recommended dose of Agrypin, the following symptoms may occur:
nausea and vomiting, involuntary muscle contractions, excitation, confusion, drowsiness, disturbances of consciousness, involuntary rapid eye movements, cardiac disorders (rapid heartbeat), coordination disturbances, psychosis with visual hallucinations, and increased excitability (see section 4. Possible side effects).

Other symptoms of a significant overdose may include: coma, severe respiratory depression, and seizures.
Accidental or intentional overdose may additionally cause symptoms within a few to several hours, such as excessive sweating, general weakness, anxiety, and tremor. Increased blood pressure, difficulty urinating, and shortness of breath may also occur.
These symptoms may subside the next day, despite the onset of liver damage, which subsequently manifests as upper abdominal discomfort, recurrence of nausea, and jaundice.

If any of the above symptoms occur, seek immediate medical attention or go to a hospital. Treatment should be carried out in a hospital setting and should include accelerating the elimination of the drug components from the body and maintaining vital functions. In case of paracetamol overdose, administration of an antidote such as N-acetylcysteine and/or methionine may be necessary. Elimination of pseudoephedrine can be accelerated by forced diuresis or dialysis. To reverse the toxic effect of dextromethorphan on the central nervous system, naloxone is used.

Children and adolescents
In case of overdose in children, serious adverse effects may occur, including neurological disturbances. Caregivers should not administer doses exceeding the recommended amount.

Missed dose of Agrypin
Agrypin is intended for temporary relief of symptoms of cold, flu, and flu-like conditions.
If a dose is missed and symptoms persist, take the next dose of Agrypin as scheduled.
Do not take a double dose to make up for a missed dose.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Frequency unknown: frequency cannot be determined from the available data

• serious condition that may cause blood acidification (so-called metabolic acidosis) in patients with severe disease taking paracetamol (see section 2);
• severe conditions affecting blood vessels in the brain, known as posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS).

Stop taking Agrypin immediately and seek immediate medical help if symptoms indicating posterior reversible encephalopathy syndrome (PRES) or reversible cerebral vasoconstriction syndrome (RCVS) occur. These include:

• sudden, severe headache,
• nausea,
• vomiting,
• confusion,
• seizures,
• visual disturbances.

Adverse reactions occurring not frequently (in 1 to 10 out of 1,000 patients taking the medicine):

• fatigue, dizziness;
• nausea and vomiting.

Adverse reactions occurring rarely (in 1 to 10 out of 10,000 patients taking the medicine):

• type I hypersensitivity reactions: allergic swelling (i.e. swelling of the skin and soft tissues, often affecting the face, e.g. lips, tongue, eyelids), anaphylactic reaction (i.e. shortness of breath, sweating, drop in blood pressure up to shock symptoms);
• skin allergic reactions, skin redness, rash.

Adverse reactions occurring very rarely (less than 1 in 10,000 patients taking the medicine):

• disturbances in blood cell production: granulocytopenia (reduced number of granulocytes in the blood), agranulocytosis (absence of granulocytes in the blood), thrombocytopenia (reduced number of platelets in the blood);
• bronchial asthma attack;
• liver damage, most commonly occurring due to overdose;
• renal colic, renal papillary necrosis, acute kidney failure, urolithiasis;
• hallucinations.

Adverse reactions with unknown frequency (frequency cannot be determined from the available data):

• drowsiness;
• increased heart rate (tachycardia);
• slight increase in blood pressure;
• disturbances in urination, urinary retention, especially in patients with benign prostatic hyperplasia;
• colitis caused by insufficient blood flow (ischemic colitis);
• reduced blood flow in the optic nerve (ischemic optic neuropathy).

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products. Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: (22) 49 21 301, fax: (22) 49 21 309, Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Agrypin

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after:
"EXP". The expiry date refers to the last day of that month.
Store below 25 °C in the original packaging. Protect from light.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Agrypin contains

• The active substances are paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide. Each coated tablet of Agrypin contains 325 mg of paracetamol, 30 mg of pseudoephedrine hydrochloride and 10 mg of dextromethorphan hydrobromide.
• The other ingredients are: microcrystalline cellulose, stearic acid, crospovidone, povidone K-25, colloidal anhydrous silica.
• Coating: lactose monohydrate, hypromellose 6 cP, titanium dioxide (E 171), macrogol 6000.

What Agrypin looks like and contents of the pack
Agrypin is a coated tablet, white to light cream in colour, oblong-shaped, with a breakline on one side.
The breakline on the tablet is not intended for breaking the tablet.
PVC/PVDC//Aluminium blisters contain 10, 12, 20 or 24 coated tablets in a cardboard box.

Marketing Authorisation Holder
Tarchomin Pharmaceutical Works "Polfa" Joint Stock Company
A. Fleminga 2 Street
03-176 Warsaw
Phone number: +48 22 811-18-14

Manufacturer
Polfarmex S.A.
Józefów 9
99-300 Kutno
Poland