Gripex forte

Package leaflet: Information for the patient

Gripex FORTE, 500 mg + 30 mg + 10 mg, coated tablets
Paracetamolum + Pseudoephedrini hydrochloridum + Dextromethorphani hydrobromidum
Please read the entire leaflet carefully before using the 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 doctor 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 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 your doctor.

Table of contents of the leaflet

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

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

Gripex Forte is a combination medicine. It contains three active substances: paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide. Paracetamol has antipyretic and analgesic effects, dextromethorphan acts as a cough suppressant, and pseudoephedrine helps restore nasal patency.
Gripex Forte 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 cold, influenza and influenza-like conditions: fever, nasal congestion, dry cough, headache, sore throat, and muscle and joint pain.
Do not use this medicine for longer than 3 days without consulting a doctor.

2. Important information before using Gripex Forte

When not to use Gripex Forte:

• if the patient is allergic to paracetamol, pseudoephedrine hydrochloride, dextromethorphan hydrobromide, or any of the other ingredients of this medicine (listed in section 6);
• if the patient is taking other medicines containing paracetamol, pseudoephedrine or dextromethorphan;
• if the patient is taking medicines from the group of MAO inhibitors (medicines used, among others, in depression), as well as within 2 weeks after discontinuation of such treatment;
• if haemolytic anaemia or congenital glucose-6-phosphate dehydrogenase deficiency is present;
• if severe liver failure is present;
• 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;
• if ischaemic heart disease is present;
• in patients with alcoholism;
• in patients with bronchial asthma;
• if respiratory failure is present or there is a risk of respiratory failure;
• during pregnancy and breastfeeding;
• in children under 12 years of age.

Warnings and precautions
Before starting treatment with Gripex Forte, discuss this with your doctor or pharmacist.
Use of this medicine may lead to dependence. Therefore, treatment should be short-term.
The medicine contains paracetamol. Do not take simultaneously with 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 simultaneously with other medicines containing dextromethorphan and pseudoephedrine.
Use of the medicine in patients with liver impairment, alcohol abuse, or malnutrition carries a risk of liver damage. Cases of liver failure have been reported in patients taking paracetamol under conditions of reduced glutathione levels, especially in severely malnourished patients, those suffering from anorexia, with low body mass index (BMI), regular alcohol drinkers, or patients with sepsis.
During treatment with Gripex Forte, immediately inform your doctor if the patient has severe conditions, including severe kidney function disorders or sepsis (when bacteria and their toxins circulate in the blood, leading to organ damage) or malnutrition, chronic alcoholism, or if the patient is also taking flucloxacillin (an antibiotic). In these situations, patients have been reported to develop a severe condition called metabolic acidosis (an abnormality in blood and body fluids), when taking paracetamol at standard doses for a prolonged 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.
Use with caution in patients with renal impairment, phaeochromocytoma, hypertension, cardiac arrhythmias, pulmonary emphysema, increased intraocular pressure, benign prostatic hyperplasia, hyperthyroidism, diabetes, patients with methemoglobin reductase deficiency, and in those taking anxiolytics, tricyclic antidepressants, other sympathomimetic medicines (e.g. decongestants, appetite suppressants), and psychostimulants similar to amphetamines.
Do not use the medicine for chronic cough with sputum production, such as that associated with cigarette smoking or bronchitis.
Do not use the medicine in patients with respiratory failure, bronchial asthma, or in patients at risk of respiratory failure.
Use the medicine with caution in patients taking anticoagulant medicines.
Due to reported cases of abuse of dextromethorphan and pseudoephedrine, particular caution should be exercised when using Gripex Forte in adolescents, young adults, and patients who abuse medicines or psychoactive substances.
Pseudoephedrine – one of the active substances in Gripex Forte – may be abused, and high doses of pseudoephedrine may be toxic. Continuous use may lead to taking higher doses of Gripex Forte than the recommended dose to achieve the desired effect, increasing the risk of overdose. Do not take a dose higher than the recommended maximum dose or exceed the duration of treatment (see section 3).
Particular caution is required in patients who are poor metabolizers of this enzyme and in patients simultaneously taking medicines that inhibit the activity of CYP2D6 (see "Gripex Forte and other medicines"), as enhanced and/or prolonged effects of dextromethorphan may occur.
Concomitant use of medicines that strongly inhibit this enzyme increases the risk of dextromethorphan poisoning, manifesting as agitation, disorientation, tremor, insomnia, diarrhoea, and respiratory depression. It may also lead to the development of life-threatening serotonin syndrome (involuntary, rhythmic muscle contractions, including muscles controlling eye movement, agitation, excessive sweating, tremor, increased reflexes, increased muscle rigidity, body temperature above 38°C). If the above symptoms occur after taking Gripex Forte, discontinue treatment immediately and seek medical advice without delay. If the patient knows they rapidly metabolize this type of medicine or previously experienced the above symptoms when taking such medicines, do not use Gripex Forte without consulting a doctor.
The medicinal product should be discontinued if neurological symptoms such as nervousness, dizziness, or insomnia occur during treatment.
Avoid using the medicinal product in patients with atopic dermatitis, as dextromethorphan may exacerbate the allergic reaction.
During treatment with Gripex Forte, sudden abdominal pain or rectal bleeding due to inflammation of the large intestine (ischaemic colitis) may occur. If such gastrointestinal symptoms occur, discontinue use of Gripex Forte and seek medical advice or medical help immediately. See section 4.
If fever with generalized skin erythema and vesicular rash occurs, discontinue taking Gripex Forte and contact a doctor or seek immediate medical help. See section 4.
During treatment with Gripex Forte, reduced blood flow in the optic nerve may occur. If sudden vision loss occurs, discontinue use of Gripex Forte and contact a doctor or seek medical help immediately. 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 that may indicate PRES or RCVS occur, discontinue use of Gripex Forte immediately and seek immediate medical help (symptoms, see section 4 "Possible side effects").
Consult your doctor even if the above warnings relate to conditions that occurred in the past.

Children
Use of the medicine in children under 12 years of age is contraindicated.

Gripex Forte and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
The interaction of Gripex Forte with other medicines results from the interactions of its active ingredients:

Paracetamol

• Do not take the medicine simultaneously with other medicines containing paracetamol.
• Medicines that accelerate gastric emptying (e.g. metoclopramide) accelerate the absorption of paracetamol.
• Medicines that delay gastric emptying (e.g. propantheline, pethidine, pentazocine, diamorphine) may delay the absorption of paracetamol.
• Concomitant 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 a state of agitation and fever.
• Concomitant 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 such as warfarin, acenocoumarol or dicoumarol).
• Concomitant use of paracetamol and medicines that increase hepatic metabolism, i.e. some sleeping medicines or antiepileptic medicines such as phenobarbital, phenytoin, carbamazepine, as well as rifampicin and isoniazid (used in the treatment of, among others, tuberculosis) may lead to liver damage, even when recommended doses of paracetamol are used.
• Paracetamol accelerates the elimination of lamotrigine from the body.
• Some medicines acting via beta-adrenergic receptors may decrease (salbutamol) or increase (propranolol) the absorption of paracetamol.
• Combined administration of an antihistamine medicine (nizatidine) with paracetamol increases the concentration of paracetamol in blood plasma.
• Caffeine enhances the analgesic effect of paracetamol.
• Concomitant administration with chloramphenicol (a broad-spectrum antibacterial antibiotic) may cause increased concentration of chloramphenicol in plasma.
• 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

• Do not take simultaneously with other medicines containing pseudoephedrine.
• Concomitant use with albuterol (used, among others, in asthma treatment) may enhance vasoconstrictive effects.
• Do not take simultaneously with amitriptyline (used, among others, in depression) and sympathomimetics (used in the treatment of bronchospasm, e.g. in asthma).
• Concomitant use with other sympathomimetics, i.e. medicines reducing congestion, 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 (e.g. aluminium hydroxide, used to relieve heartburn and indigestion) may increase the 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 effect of cardiac glycosides (used in heart failure).
• Do not take simultaneously with furazolidone (an antibacterial medicine).

Dextromethorphan

• Do not take simultaneously with other medicines containing dextromethorphan.
• Do not take with MAO inhibitors (medicines used in depression treatment).
• Dextromethorphan may enhance the effect of alcohol, antihistamines, and psychotropic medicines on the central nervous system.
• Combined administration of dextromethorphan with non-steroidal anti-inflammatory drugs such as ketorolac and tenoxicam may enhance their analgesic effect.
• Limit the dose and duration of use when taking opioids and sedatives concomitantly due to the risk of excessive sedation, respiratory depression, coma, or death.
• Medicines that reduce the activity of the CYP2D6 enzyme, such as: fluoxetine, paroxetine, quinidine, terbinafine, amiodarone, flecainide, propafenone, sertraline, bupropion, methadone, cinacalcet, haloperidol, perphenazine, and thioridazine may increase the blood concentration of dextromethorphan (see "Warnings and precautions").

Gripex Forte with food, drink or alcohol
Do not drink alcohol during treatment. Drinking alcohol while taking paracetamol leads to the formation of a toxic metabolite causing necrosis of liver cells, which may subsequently lead to liver failure.

Pregnancy and breastfeeding
Use of Gripex Forte during pregnancy and breastfeeding is contraindicated.

Driving and operating machinery
During treatment, exercise caution when driving and operating machinery due to the possibility of dizziness and drowsiness.

Gripex Forte contains tartrazine, lac (E 102).
The medicine may cause allergic reactions.

3. How to use Gripex Forte

This medicine should always be taken exactly as described in the patient leaflet or as directed by a doctor or pharmacist. If in doubt, consult a doctor or pharmacist.
Gripex Forte should be taken orally.
Recommended dose
Adults and adolescents aged 12 years and above: 1 or 2 tablets, which may be repeated every 4 to 6 hours as needed, up to 3 or 4 times daily.
Do not exceed 8 tablets in 24 hours.
Do not use the medicine for longer than 3 days without consulting a doctor.
Do not exceed the recommended dose. Use the lowest effective dose for the shortest possible duration.

Overdose of Gripex Forte
Seek immediate medical advice. The medicine contains three active substances. Symptoms of overdose may result from one or all of the active substances.
Overdose may cause, within a few to several hours, symptoms such as nausea, vomiting, dilated pupils, excessive sweating, drowsiness, general weakness, restlessness, tremor.
Nystagmus, increased blood pressure, rapid heartbeat, seizures, difficulty urinating, and shortness of breath may also occur. These symptoms may resolve the following day, despite the onset of potentially life-threatening liver damage, which subsequently manifests as upper abdominal discomfort, recurrence of nausea, and jaundice. Overdose may also lead to:
coagulation disorders (blood clotting and bleeding). In case of overdose, seek immediate medical help. Treatment of overdose should be carried out in a hospital and involves accelerating the elimination of the drug components from the body and maintaining vital functions. In case of paracetamol overdose, an antidote such as N-acetylcysteine and (or) methionine may be required.

Missed dose of Gripex Forte
Gripex Forte is intended for temporary 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 taking Gripex Forte immediately and seek immediate medical attention 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.

If any of the following side effects occur, contact a doctor immediately or seek urgent medical help:

• 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) (rare);
• skin allergic reactions, skin redness, rash (rare);
• severe skin reactions (very rare with paracetamol), including sudden fever, skin redness, or numerous small pustules (possible symptoms of acute generalized exanthematous pustulosis - AGEP; frequency unknown with pseudoephedrine), which may occur within the first 2 days of using Gripex Forte. See "Warnings and precautions" in section 2.
• bronchial asthma attack (very rare);
• liver damage, most commonly due to overdose (very rare);
• renal colic, necrosis of renal papillae, acute renal failure (very rare);
• urinary disorders, urinary retention, especially in patients with benign prostatic hyperplasia (very rare);
• colitis of the large intestine due to insufficient blood supply (ischemic colitis of the large intestine) (see also "Warnings and precautions").

Other side effects:
Side effects occurring not very commonly (less than 1 in 100 patients using the medicine):

• fatigue.

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

• nausea and vomiting.

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

• blood cell formation disorders: granulocytopenia (reduced number of granulocytes in blood), agranulocytosis (absence of granulocytes in blood), thrombocytopenia (reduced number of platelets in blood);
• kidney stones.

Side effects with unknown frequency (cannot be estimated from available data):

• serious conditions affecting brain blood vessels, known as posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS);
• dizziness;
• drowsiness;
• hallucinations (especially in children);
• rapid heartbeat (tachycardia);
• slight increase in blood pressure;
• reduced blood flow in the optic nerve (ischemic 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 side effects occur, including those 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
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.
Reporting side effects helps provide more information on the safety of the medicine.

5. How to store Gripex Forte

Do not store above 25°C.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and immediate packaging (month/year). The expiry date refers to the last day of the stated month.
Blister pack labeling: EXP - expiry date, Lot - batch number.
Do not dispose of medicines via the sewage system 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 Gripex FORTE contains:

• The active substances in this medicine are paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide. Each coated tablet contains 500 mg of paracetamol, 30 mg of pseudoephedrine hydrochloride and 10 mg of dextromethorphan hydrobromide.
• Other ingredients are: Tablet core: povidone K30, pregelatinized starch (corn), crospovidone (type A), microcrystalline cellulose, stearic acid 50, anhydrous colloidal silicon dioxide. Coating: hypromellose type 2910, 6 mPas, titanium dioxide (E 171), tartrazine, aluminium lake (E 102), macrogol 400. Printing ink: shellac, iron oxide black (E 172), n-butyl alcohol, isopropyl alcohol, ammonium hydroxide, propylene glycol.

What Gripex FORTE looks like and contents of the pack
Yellow, round, film-coated tablets with a black print "Gripex F" on one side.
Each tablet measures approximately 12 mm x 8 mm.
Pack sizes available:
10 tablets (1 blister containing 10 tablets);
20 tablets (2 blisters containing 10 tablets each).
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
US Pharmacia Sp. z o.o.
Ziębicka Street 40
50-507 Wrocław, Poland
For further information about this medicine, please contact the representative of the Marketing Authorisation Holder:
USP Zdrowie Sp. z o.o.
Poleczki Street 35
02-822 Warsaw, Poland
Tel.: +48 (22) 543 60 00