Gripex max

Package leaflet: Information for the patient

GRIPEX MAX, 500 mg + 30 mg + 15 mg, film-coated tablets
Paracetamolum + Pseudoephedrini hydrochloridum + Dextromethorphani hydrobromidum
Please read the entire leaflet carefully before using this medicine, as it contains
important information for the patient.
This medicine should always be used exactly as described 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, please consult your pharmacist.
• If you experience any adverse reactions, including any possible side effects 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, consult your doctor.

Contents of the leaflet

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

1. What Gripex Max is and what it is used for

Gripex Max is a combination medicine. It contains three active substances: paracetamol, pseudoephedrine, and dextromethorphan. Paracetamol has antipyretic and analgesic effects, dextromethorphan acts as a cough suppressant, and pseudoephedrine helps restore nasal patency. Gripex Max is intended for use in adults and adolescents over 12 years of age. It is indicated for the short-term treatment of severe symptoms of the common cold, influenza, and influenza-like conditions, such as fever, headache, sore throat, muscle and joint pain, nasal congestion, and dry cough.

2. Important information before using Gripex Max

Use of this medicine may lead to dependence. Therefore, treatment should be short-term.

When not to use Gripex Max:

• if the patient is allergic to paracetamol, hydrochloride of pseudoephedrine, hydrobromide of dextromethorphan, or any of the other ingredients of this medicine (listed in section 6);
• if the patient is taking other medicines containing paracetamol;
• if the patient is taking MAO inhibitor drugs (medicines used, among others, in depression), or within 2 weeks after discontinuation of such treatment;
• in case of congenital glucose-6-phosphate dehydrogenase deficiency;
• in case of severe liver impairment;
• if the patient has very high blood pressure (severe hypertension) or hypertension that cannot be controlled with medication;
• if the patient has severe acute (sudden) or chronic (long-term) kidney disease or kidney failure;
• in case of ischemic heart disease;
• in patients with alcoholic disease;
• in patients with bronchial asthma;
• during pregnancy and breastfeeding;
• in children under 12 years of age.

Warnings and precautions

Before starting to use Gripex Max, consult a doctor or pharmacist.

The medicine contains paracetamol. Do not take other medicines containing paracetamol (e.g., some medicines used to relieve cold and flu symptoms) due to the risk of overdose and associated life-threatening liver damage. Prolonged or frequent use of the medicine is not recommended.

Do not exceed the recommended daily dose. In case of overdose, contact a doctor immediately, even if the patient feels well. See also section 3 "Use of a higher than recommended dose of Gripex Max".

Use of the medicine in patients with liver impairment, alcohol abuse, or starvation carries a risk of liver damage. Use with caution in patients with renal impairment, hypertension, cardiac arrhythmias, pulmonary emphysema, increased intraocular pressure, benign prostatic hyperplasia, hyperthyroidism, diabetes, and in patients taking anxiolytics, tricyclic antidepressants, other sympathomimetic drugs (e.g., decongestants, appetite suppressants), and psychostimulants similar to amphetamines.

Do not use this medicine for 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. Do not drink alcohol while taking this medicine.

Due to reported cases of dextromethorphan abuse, particular caution should be exercised when using Gripex Max in adolescents, young adults, and patients who abuse drugs or psychoactive substances.

Exercise special caution in patients who are poor metabolizers via the CYP2D6 enzyme or who are taking substances that inhibit CYP2D6 enzyme activity (listed in section "Gripex Max and other medicines"). If taking medicines that inhibit CYP2D6 enzyme activity, consult a doctor before using this medicine. If simultaneous use of CYP2D6 inhibitors and dextromethorphan is necessary, the patient must be under strict medical supervision. Dose reduction of dextromethorphan may be required.

In patients who are poor metabolizers of this enzyme and in patients concurrently taking CYP2D6-inhibiting drugs, enhanced and/or prolonged effects of dextromethorphan may occur. Concurrent use of drugs strongly inhibiting this enzyme increases the risk of dextromethorphan toxicity, manifesting as excitation, disorientation, tremor, insomnia, diarrhea, and respiratory depression. It may also lead to the development of life-threatening serotonin syndrome (rapid heartbeat, disorientation, profuse sweating, hallucinations, involuntary muscle movements, chills, tremors). If the above symptoms occur after taking Gripex Max, discontinue treatment immediately and seek medical advice without delay.

If the patient develops fever with generalized skin redness and blistering rash, discontinue use of Gripex Max and contact a doctor or seek immediate medical help. See section 4.

During treatment with Gripex Max, inform the doctor immediately if the patient develops severe illnesses, including severe kidney function disorders 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 have developed a serious condition called metabolic acidosis (abnormality in blood and body fluids), when paracetamol was taken regularly for a prolonged period or when paracetamol was taken together with flucloxacillin. Symptoms of metabolic acidosis may include: severe breathing difficulties, including rapid deep breathing, drowsiness, nausea, and vomiting.

During use of Gripex Max, sudden abdominal pain or rectal bleeding due to inflammation of the large intestine (ischemic colitis) may occur. If such gastrointestinal symptoms occur, discontinue use of Gripex Max and seek immediate medical advice or medical help. See section 4.

During use of Gripex Max, reduced blood flow in the optic nerve may occur. If sudden vision loss occurs, discontinue use of Gripex Max and contact a doctor or seek immediate medical help. See section 4.

Cases of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) have been reported after use of medicines containing pseudoephedrine.

PRES and RCVS are rare conditions that may be associated with reduced blood flow to the brain.

If symptoms occur that may indicate PRES or RCVS, discontinue use of Gripex Max immediately and seek immediate medical help (symptoms, see section 4 "Possible side effects").

If the patient is taking medicines such as certain antidepressants or antipsychotics, Gripex Max may interact with them, causing changes in mental state (e.g., excitation, 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).

If symptoms worsen or do not improve within 3 days, contact a doctor.

Consult a doctor, even if the above warnings refer to conditions that occurred in the past.

Children

Do not use this medicine in children under 12 years of age.

Gripex Max and other medicines

Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines you plan to take.

Interactions of Gripex Max with other medicines result from the interactions of the active substances in the medicine:

Paracetamol

• Do not use this medicine simultaneously with other medicines containing paracetamol.
• Medicines that accelerate gastric emptying (e.g., metoclopramide) increase the absorption rate of paracetamol.
• Medicines that delay gastric emptying (e.g., propantheline) may delay the absorption of paracetamol.
• Concurrent use of paracetamol with MAO inhibitors (used in the treatment of, among others, depression) and within 2 weeks after discontinuation of such treatment may cause excitation and fever.
• Concurrent use of paracetamol with zidovudine (AZT, a medicine used in HIV infection) may enhance the toxic effect of zidovudine on bone marrow.
• Paracetamol may enhance the effect of anticoagulant medicines (coumarin derivatives).
• Concurrent use of paracetamol with medicines 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.
• Drinking alcohol during paracetamol treatment leads to the formation of a toxic metabolite causing necrosis of liver cells, which may subsequently lead to liver failure.
• Concomitant administration with chloramphenicol (a broad-spectrum antibacterial antibiotic) may increase chloramphenicol plasma concentration.
• Inform your doctor or pharmacist if you are taking flucloxacillin (an antibiotic), due to the serious risk of blood and body fluid disorders (called metabolic acidosis), which must be urgently treated (see section 2).

Pseudoephedrine

• Concurrent use with albuterol (used, among others, in asthma treatment) may enhance vasoconstrictive effects.
• Do not use simultaneously with amitriptyline (used, among others, in depression) or other sympathomimetics (used in bronchospasm treatment, e.g., in asthma).
• Concurrent use with other sympathomimetics, such as decongestants, appetite suppressants, or substances with psychostimulant effects similar to amphetamines, may cause increased blood pressure.
• Ammonium chloride, by alkalinizing urine, increases renal reabsorption of pseudoephedrine metabolites and prolongs its duration of action.
• Antacids (used to relieve heartburn and indigestion) may increase absorption of pseudoephedrine.
• MAO inhibitors (used in depression treatment) cause slower elimination of pseudoephedrine from the body and increase its bioavailability.
• Pseudoephedrine reduces the effect of antihypertensive medicines and may modify the action of cardiac glycosides (used in heart failure).
• Do not use simultaneously with furazolidone (an antibacterial medicine).

Dextromethorphan

• Do not use with MAO inhibitors (medicines used in depression treatment).
• Medicines that reduce CYP2D6 enzyme activity, such as: fluoxetine, paroxetine, quinidine, terbinafine, amiodarone, flecainide, propafenone, sertraline, bupropion, methadone, cinacalcet, haloperidol, perphenazine, and thioridazine, may increase blood levels of dextromethorphan.

Gripex Max with food, drink, or alcohol

Food does not significantly affect absorption of the medicine.

Do not drink alcohol during treatment with this medicine.

Pregnancy and breastfeeding

Use of Gripex Max during pregnancy and breastfeeding is contraindicated.

Driving and operating machinery

Exercise caution when driving vehicles or operating machinery while taking Gripex Max.

Gripex Max contains tartrazine, lac (E 102).

The medicine may cause allergic reactions.

3. How to use Gripex Max

This medicine should always be used exactly as described in the patient leaflet or as directed by a doctor or pharmacist. If in doubt, consult a doctor or pharmacist.
Gripex Max should be taken orally.
Recommended dose
Adults and adolescents over 12 years of age: 1 to 2 tablets, 3–4 times daily.
Do not exceed 8 tablets per day.
Taking more than the recommended dose of Gripex Max
Seek immediate medical advice from a doctor or pharmacist. The medicine contains three active substances.
Symptoms of overdose may result from the action of one or all of the active substances.
If a patient takes more than the recommended dose of Gripex Max, the following symptoms may occur within a few to several hours: nausea, vomiting, involuntary muscle spasms, excessive sweating, restlessness, increased excitability, confusion, drowsiness, general weakness, anxiety, tremor, disturbances in consciousness, involuntary rapid eye movements, nystagmus, elevated blood pressure, cardiovascular disorders (rapid heartbeat), coordination disturbances, psychosis with visual hallucinations, difficulty urinating, and shortness of breath.
Other symptoms of severe overdose may include: coma, severe respiratory depression, and seizures.
These symptoms may subside the following day, despite the onset of potentially life-threatening liver damage, which subsequently manifests as upper abdominal discomfort, recurrence of nausea, and jaundice.
In case of overdose or if any of the above symptoms occur, seek immediate medical attention or go to hospital.
Treatment of overdose with Gripex Max should be conducted in a hospital.
It involves accelerating the elimination of the drug components from the body and maintaining vital functions. In case of paracetamol overdose, administration of an antidote may be necessary: N-acetylcysteine and (or) methionine.
Missing a dose of Gripex Max
Gripex Max is intended for short-term relief of cold, flu, and flu-like symptoms. If a dose is missed and symptoms persist, take the next dose as scheduled. Do not take a double dose to make up for a missed dose.

4. Possible side effects

Like all medicines, this medicine may cause side effects, although not everybody gets them.
Stop using Gripex Max immediately and seek immediate medical help if symptoms indicating posterior reversible encephalopathy syndrome (PRES) or reversible cerebral vasoconstriction syndrome (RCVS) occur:

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

Side effects occurring not very often (in 1 to 10 out of 1,000 patients using the medicine):

• fatigue, dizziness;
• nausea and vomiting.

Side effects occurring rarely (in 1 to 10 out of 10,000 patients using 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, low blood pressure up to shock symptoms);
• skin allergic reactions, skin redness, rash.

Side effects occurring very rarely (less than 1 in 10,000 patients using the medicine):

• blood cell production disorders: granulocytopenia (reduced number of granulocytes in blood), agranulocytosis (absence of granulocytes in blood), thrombocytopenia (reduced number of platelets in blood);
• asthma attack;
• liver damage, most commonly due to overdose;
• renal colic, necrosis of renal papillae, acute kidney failure, urinary stones;
• hallucinations.

Side effects with unknown frequency (frequency cannot be estimated from available data):
­ severe conditions affecting cerebral blood vessels, known as posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS);
­ drowsiness;
­ increased heart rate (tachycardia);
­ slight increase in blood pressure;
­ difficulty urinating, urinary retention, especially in patients with benign prostatic hyperplasia;
­ colitis due to inadequate blood supply (ischaemic colitis);
­ sudden fever, skin redness, or numerous small pustules (possible symptoms of acute generalized exanthematous pustulosis - AGEP) may occur within the first 2 days of using Gripex Max. See section 2.
If such symptoms occur, discontinue use of Gripex Max and contact a doctor or seek immediate medical help;

• reduced blood flow in the optic nerve (ischaemic optic neuropathy);
• serious condition that may cause blood acidification (so-called metabolic acidosis) in patients with severe illness taking paracetamol (see section 2).

Reporting of side effects
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +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.
Reporting side effects helps provide more information on the safety of the medicine.

5. How to store Gripex Max

Medicine packed in containers or sachets in a cardboard box: no special storage conditions required.
Medicine packed in blisters in a cardboard box: do not store above 25°C.
Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and immediate packaging (month/year). The expiry date refers to the last day of the stated month.
Blister labelling: EXP – expiry date, Lot – batch number.
Do not dispose of medicines via the sewage system or household waste.
Ask your pharmacist what to do with unused medicines.
This will help protect the environment.

6. Contents of the package and other information

What Gripex Max contains:

• The active substances are paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide. Each film-coated tablet contains 500 mg of paracetamol, 30 mg of pseudoephedrine hydrochloride and 15 mg of dextromethorphan hydrobromide.
  Other ingredients are:

Tablet core:
povidone, microcrystalline cellulose, pregelatinized starch, crospovidone, colloidal anhydrous silica,
stearic acid.
Coating:
(yellow coating system): hypromellose, titanium dioxide (E 171), tartrazine, lac (E 102),
macrogol 400.
Printing ink:
(Opacode Black S-1-17823): shellac, iron oxide black (E 172), n-butyl alcohol, isopropyl alcohol,
ammonium hydroxide, propylene glycol.
Carnauba wax.

What Gripex Max looks like and contents of the pack:
Yellow, round, film-coated tablets with black print "Gripex M" on one side.

Pack sizes available:
PVC/PVDC/Aluminium foil blisters in cardboard carton:
6 tablets (1 blister with 6 tablets);
10 tablets (1 blister with 10 tablets);
12 tablets (1 blister with 12 tablets);
20 tablets (2 blisters with 10 tablets each).

Paper/PE/Aluminium/PE laminate sachets in cardboard carton:
6 tablets (3 sachets with 2 tablets each).

HDPE bottle with HDPE screw cap in cardboard carton:
20 tablets (1 bottle with 20 tablets).

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:
US Pharmacia Sp. z o.o.
ul. Ziębicka 40
50-507 Wrocław
For further information, please contact:
USP Zdrowie Sp. z o.o.
ul. Poleczki 35
02-822 Warszawa
tel.: +48 (22) 543 60 00