Gripex day and night

Package leaflet: information for the patient

Gripex DAY and NIGHT
500 mg + 30 mg + 15 mg, coated tablets
Paracetamolum + Pseudoephedrini hydrochloridum + Dextromethorphani hydrobromidum
500 mg + 30 mg + 15 mg + 2 mg, coated tablets
Paracetamolum + Pseudoephedrini hydrochloridum + Dextromethorphani hydrobromidum +
Chlorphenamini maleas
Please read the entire leaflet carefully before taking this medicine, as it contains important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any further questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse (see section 4).

Leaflet contents

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

1. What is Gripex DAY and NIGHT and what is it used for

Gripex DAY and NIGHT is a combination medicine. The tablet (yellow) "for the day" contains three active substances:
paracetamol, pseudoephedrine hydrochloride, and dextromethorphan. The tablet (blue) "for the night" additionally contains chlorphenamine. Paracetamol reduces fever and relieves pain, dextromethorphan suppresses cough, pseudoephedrine hydrochloride reduces nasal mucosal congestion, and chlorphenamine relieves runny nose.
Gripex DAY and NIGHT is used for the short-term treatment of symptoms of cold, influenza, and influenza-like conditions (fever, runny nose, nasal congestion, dry cough, headache and sore throat, muscle pain, bone and joint pain), including symptoms occurring before sleep that interfere with falling asleep, in adults during the day and at night.

2. Important information before using Gripex DAY and NIGHT

This medicine may lead to dependence. Therefore, treatment should be short-term. The patient should consult a doctor if symptoms worsen or do not improve after 3 days.

When not to use Gripex DAY and NIGHT

• if the patient is allergic to the active substances 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 medicines called monoamine oxidase inhibitors (MAOIs), or if less than 2 weeks have passed since stopping their use;
• if the patient has been diagnosed with glucose-6-phosphate dehydrogenase deficiency (an inherited red blood cell disorder);
• if the patient has severe liver function impairment;
• if the patient has very high blood pressure (severe hypertension) or uncontrolled hypertension;
• if the patient has severe acute (sudden) or chronic (long-term) kidney disease or kidney failure;
• if the patient has severe ischemic heart disease;
• if the patient has severe circulatory system disorders;
• if the patient regularly consumes alcohol or is alcohol-dependent;
• if the patient has respiratory failure or is at risk of respiratory failure (e.g., in patients with chronic obstructive pulmonary disease, pneumonia, during an asthma attack, or with asthma exacerbation);
• if the patient has glaucoma (increased intraocular pressure);
• if the patient is using other vasoconstrictor medicines to relieve nasal mucosal swelling, administered orally or intranasally (e.g., phenylpropanolamine, phenylephrine, and ephedrine), or methylphenidate;
• if the patient has previously suffered a stroke or currently has risk factors for stroke;
• if the patient has benign prostatic hyperplasia;
• if the patient has had a myocardial infarction;
• if the patient has a pheochromocytoma (a rare adrenal gland tumor);
• if the patient has diabetes;
• if the patient has hyperthyroidism (a condition in which the thyroid gland produces too much hormone);
• if the patient is pregnant or breastfeeding;
• if the patient is under 18 years of age.

Warnings and precautions

Before starting treatment with Gripex DAY and NIGHT, discuss it with a doctor or pharmacist.

During treatment with Gripex DAY and NIGHT, immediately inform a doctor if the patient has severe diseases, 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 these situations, severe illness called metabolic acidosis (a blood and fluid imbalance) has been reported in patients who took paracetamol regularly for a prolonged period or took paracetamol together with flucloxacillin. Symptoms of metabolic acidosis may include: severe breathing difficulties, including rapid deep breathing, drowsiness, nausea, and vomiting.

This medicine may damage the liver in people with liver failure, those who abuse alcohol, or those who are starved or dehydrated. Patients should exercise caution when using this medicine if they suffer from kidney failure, hypertension, cardiac arrhythmias, pulmonary emphysema, or if they are taking anxiolytics, antidepressants (tricyclic antidepressants, e.g., amitriptyline), nasal decongestants, appetite suppressants, or psychostimulants (vasoconstrictive sympathomimetic drugs and amphetamine-like psychostimulants).

This medicine should not be used in patients with chronic cough accompanied by sputum production.

This medicine contains chlorphenamine and should not be used in patients with long QT syndrome (a cardiac arrhythmia) until its safety has been proven in this high-risk group. Due to this substance, this medicine should be used with caution in patients with epilepsy.

Gripex DAY and NIGHT tablets (blue) "for night" contain chlorphenamine and should be used cautiously in elderly patients due to an increased risk of nervous system adverse effects.

Use with caution if the patient is taking anticoagulant medicines. In such patients, it is recommended to reduce the therapeutic dose by half. Alcohol should not be consumed during treatment with this medicine.

Gripex DAY and NIGHT should be used with particular caution in adults taking psychoactive medicines or substances, especially if there is evidence of dextromethorphan abuse.

Exercise caution in patients whose body produces low levels of an enzyme called CYP2D6 or if they are taking substances that may reduce the activity of this enzyme (listed in section "Gripex DAY and NIGHT and other medicines"). If the patient is taking medicines that inhibit CYP2D6 enzyme activity, they should consult a doctor before using this medicine. If simultaneous use of CYP2D6 inhibitors and dextromethorphan is necessary, the patient's condition should be monitored by a doctor. A reduction in the dextromethorphan dose may be required.

In patients with poor CYP2D6 metabolism and in patients taking CYP2D6 inhibitors concurrently, the effect of dextromethorphan may be stronger and/or longer. Therefore, there is a risk of dextromethorphan toxicity (manifesting as agitation, confusion, tremors, insomnia, diarrhea, and respiratory depression), which may lead to serotonin syndrome (increased heart rate, disorientation, profuse sweating, hallucinations, involuntary muscle movements, chills, tremors). If any of the above symptoms occur after taking Gripex DAY and NIGHT, the medicine should be discontinued immediately and the patient should contact a doctor or seek medical help without delay.

Pseudoephedrine—one of the active substances in Gripex DAY and NIGHT—may be abused, and high doses of pseudoephedrine may be toxic. Continuous use may lead to taking higher doses of Gripex DAY and NIGHT than the recommended dose to achieve the desired effect, increasing the risk of overdose. Do not exceed the recommended maximum dose or treatment duration (see section 3).

If the patient develops fever with generalized skin redness and blistering rash, stop taking Gripex DAY and NIGHT and contact a doctor or seek immediate medical help. See section 4.

During treatment with Gripex DAY and NIGHT, sudden abdominal pain or rectal bleeding due to inflammation of the large intestine (ischemic colitis) may occur. If such gastrointestinal symptoms occur, stop taking Gripex DAY and NIGHT immediately and seek medical advice or help without delay. See section 4.

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

If the patient is taking medicines such as certain antidepressants or antipsychotics, Gripex DAY and NIGHT may interact with them, causing changes in mental state (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).

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 Gripex DAY and NIGHT and seek immediate medical help (symptoms, see section 4 "Possible side effects").

If there is no improvement after 3 days or if the patient feels worse, contact a doctor.

Talk to a doctor, even if the above symptoms occurred in the past.

The maleate salt of chlorphenamine contained in the tablet (blue) "for night" causes drowsiness; therefore, the "night" tablet should be taken only before bedtime.

Children

Use of Gripex DAY and NIGHT is contraindicated in individuals under 18 years of age.

Gripex DAY and NIGHT and other medicines

Inform your doctor or pharmacist about all medicines currently used, recently used, or planned for use.

The interaction of Gripex DAY and NIGHT with other medicines results from the effects of its active ingredients:

Paracetamol

• Concomitant use of this medicine with other medicines containing paracetamol is contraindicated.
• Medicines that accelerate gastric emptying (e.g., metoclopramide) increase the absorption of paracetamol.
• Medicines that delay gastric emptying (e.g., propantheline) may delay paracetamol absorption.
• Concomitant use of paracetamol with monoamine oxidase inhibitors [MAOIs] (used to treat depression) and within 2 weeks after stopping such treatment may cause agitation 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 antiepileptics (e.g., phenobarbital, phenytoin, carbamazepine, and rifampicin [used, e.g., in tuberculosis treatment]) may lead to liver damage even when recommended therapeutic doses of paracetamol are used.
• Alcohol consumption during paracetamol treatment leads to the formation of a toxic metabolite that causes liver cell death, potentially leading to liver failure.
• Inform the doctor or pharmacist if the patient is taking flucloxacillin (an antibiotic) due to the serious risk of blood and body fluid disorders (called metabolic acidosis), which require urgent treatment (see section 2).

Pseudoephedrine

• Concurrent use with albuterol (used in asthma treatment) may increase heart rate, raise systolic or diastolic blood pressure, and cause ECG changes.
• Do not use simultaneously with amitriptyline (used, e.g., for depression) or sympathomimetics (used in bronchoconstriction treatment, e.g., in asthma).
• Concurrent use of other sympathomimetics, such as nasal decongestants (medicines relieving nasal mucosal congestion), appetite suppressants, or amphetamine-like psychostimulants, may increase blood pressure.
• Ammonium chloride increases renal absorption of pseudoephedrine metabolites and prolongs its effect.
• Antacids (used for heartburn and indigestion) may increase pseudoephedrine absorption.
• MAO inhibitors (used in depression treatment) may enhance the effect of pseudoephedrine, potentially leading to hypertensive crisis (sudden, severe increase in blood pressure) and bradycardia (slow heart rate).
• Pseudoephedrine reduces the effect of antihypertensive medicines and may modify the effect of digitalis glycosides (used in heart failure).

Dextromethorphan

• Do not use with MAO inhibitors (medicines used in depression treatment).
• 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 dextromethorphan serum concentration.

Chlorphenamine

• MAO inhibitors (medicines used in depression treatment) may prolong and intensify the anticholinergic and central nervous system depressant effects of antihistamines.
• Literature has reported a case of polymorphic ventricular tachycardia of the torsade de pointes type (a specific type of cardiac arrhythmia) induced by chlorphenamine in a patient taking long-term thioridazine (an antipsychotic medicine).
• Chlorphenamine inhibits the metabolism of phenytoin (an antiepileptic medicine) and may lead to phenytoin toxicity.
• Antihistamines may enhance the effects of alcohol and other substances that depress the central nervous system.
• Medicines that alter urine pH, such as ammonium chloride, sodium bicarbonate, mandelic acid, hippuric acid, ascorbic acid, and antacids, cause significant changes in chlorphenamine excretion. Acidification of urine increases chlorphenamine excretion, while alkalinization of urine decreases its excretion.

Use of Gripex DAY and NIGHT with food, drink, and alcohol

Generally, food does not significantly affect the absorption of this medicine.

Do not consume alcohol during treatment with this medicine.

Do not take this medicine simultaneously with grapefruit juice or bitter orange juice.

Pregnancy and breastfeeding

Use of this medicine is contraindicated during pregnancy and breastfeeding.

Driving and operating machinery

Do not drive or operate machinery while using this medicine.

The tablet (yellow) "for day" contains tartrazine (E102).

Tartrazine may cause allergic reactions.

3. How to use Gripex DAY and NIGHT

This medicine should always be taken according to the doctor's instructions. If in doubt, consult a
doctor or pharmacist.
Gripex DAY and NIGHT is intended for oral administration.
Adults
Do not take more than 8 tablets per day.
Yellow tablet "for the day": 1-2 tablets 2-3 times daily. Do not take more than 6 tablets per day.
Blue tablet "for the night": 1-2 tablets before bedtime (do not take more than 2 tablets per day).
In elderly patients, the recommended initial dose of the blue "night" tablet should be 1 tablet.
Tablets should be swallowed with water.
The blue "night" tablet should only be taken before bedtime.
Do not use this medicine for longer than 3 days.
Taking more than the recommended dose of Gripex DAY and NIGHT
Contact a doctor or pharmacist immediately. Symptoms of overdose may be caused by one or all of the active substances. If a patient takes more than the recommended dose of Gripex DAY and NIGHT within several or more hours, the following symptoms may occur:
nausea, vomiting, involuntary muscle contractions, excessive sweating, stimulation, increased excitability, confusion, drowsiness, general weakness, restlessness, tremor, disturbances of consciousness, involuntary rapid eye movements, nystagmus, high blood pressure, cardiac disorders (rapid heartbeat), lack of coordination, psychosis with visual hallucinations, difficulty urinating, and shortness of breath.
Other symptoms of overdose may include: coma, severe respiratory depression, and seizures.
These symptoms may resolve the next day, despite the onset of liver damage, which subsequently manifests as upper abdominal discomfort (bloating), recurrence of nausea, and jaundice.
Overdose may also lead to coagulation disorders (blood clotting and bleeding).
If any of the above symptoms occur, seek medical attention immediately or go to hospital.
Treatment of overdose with Gripex DAY and NIGHT should be carried out in a hospital.
It involves accelerating the elimination of the drug from the body and maintaining vital functions. In case of paracetamol overdose, administration of an antidote may be necessary: N-acetylcysteine and (or) methionine.
Missed dose of Gripex DAY and NIGHT
Gripex DAY and NIGHT is used 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 Gripex DAY and NIGHT as scheduled. Do not take a double dose to make up for a missed dose.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
You must stop taking Gripex DAY and NIGHT immediately and seek medical help immediately if symptoms
indicative of posterior reversible encephalopathy syndrome (PRES) or reversible cerebral vasoconstriction
syndrome (RCVS) occur. These include:

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

Common adverse effects (may occur in less than 1 in 10 people):

• facial dyskinesia, coordination disorders (rigidity), tremor, paresthesia (numbness, tingling sensation);
• blurred vision, double vision;
• dryness of nasal and oral mucous membranes, dryness of mucous membranes;
• dry mouth, nausea, taste disturbances, diarrhea;
• excessive sweating;
• urinary retention and (or) difficulty in passing urine.

Uncommon adverse effects (may occur in less than 1 in 100 people):

• fatigue, dizziness.

Rare adverse effects (may occur in less than 1 in 1,000 people):

• type I hypersensitivity reactions: allergic edema (i.e. swelling of the skin and soft tissues, often affecting the face, such as lips, tongue, eyelids), anaphylactic reaction (i.e. shortness of breath, sweating, drop in blood pressure with signs of shock);
• allergic skin reactions, erythema, rash, itching, sweating, roseola, urticaria;
• blood cell count changes (agranulocytosis – dangerously low number of white blood cells called granulocytes; leukopenia – reduced number of white blood cells called leukocytes; aplastic anemia – a condition in which the bone marrow does not produce enough blood cells; thrombocytopenia – reduced number of blood cells called platelets), with symptoms such as unusual bleeding or fatigue.

Very rare adverse effects (may occur in less than 1 in 10,000 people):

• abnormal blood test results: granulocytopenia (reduced number of blood cells called granulocytes), agranulocytosis, thrombocytopenia;
• asthma attack;
• liver damage, usually due to overdose;
• renal colic, necrosis of renal papillae, acute kidney failure;
• hallucinations;
• dizziness;
• acute and chronic pancreatitis, bleeding;
• severe skin reactions, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis.

Unknown frequency (cannot be estimated from available data):

• serious conditions affecting cerebral blood vessels, known as posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS);
• increased heart rate (tachycardia);
• elevated blood pressure;
• low blood pressure;
• increased thirst;
• urinary retention;
• urinary disorders, urinary retention, especially in patients with enlarged prostate;
• ischemic colitis (inflammation of the large intestine due to inadequate blood supply);
• sudden fever, skin redness, or multiple small pustules (possible symptoms of acute generalized exanthematous pustulosis - AGEP) may occur within the first 2 days of taking Gripex DAY and NIGHT. See section 2. If these symptoms occur, discontinue use of Gripex DAY and NIGHT and contact a doctor or seek immediate medical help;
• reduced blood flow in the optic nerve (ischemic optic neuropathy);
• unexpected excitation may occur, particularly after administration of high doses in children or elderly patients, or in patients with anxiety disorders, insomnia, nervousness, or delirium;
• impotence, intermenstrual bleeding;
• a serious condition that may cause blood acidification (so-called metabolic acidosis) in patients with severe illness taking paracetamol (see section 2).

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform 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, phone: +48 22 49 21 301, fax: +48 22 49 21 309, website:
https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the responsible entity.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Gripex DAY and NIGHT

Do not store above 25°C. Keep the blister in the outer packaging to protect from light.
This medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister marked "EXP". The expiry date refers to the last day of the stated month.
Medicines should not be disposed of 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 DAY and NIGHT contains
Tablet (yellow) "for day":
The active substances are:
Paracetamol 500 mg
Pseudoephedrine hydrochloride 30 mg
Dextromethorphan hydrobromide 15 mg
The other excipients are:
Tablet core:
Povidone K-30, microcrystalline cellulose, crospovidone (type A), pregelatinized corn starch, stearic acid, anhydrous colloidal silica
Tablet coating:
(Opadry Yellow): hypromellose (2910) 6cP, titanium dioxide (E171), tartrazine (E102), polyethylene glycol 400.

Tablet (blue) "for night":
The active substances are:
Paracetamol 500 mg
Pseudoephedrine hydrochloride 30 mg
Dextromethorphan hydrobromide 15 mg
Chlorpheniramine maleate 2 mg
The other excipients are:
Tablet core:
Pregelatinized corn starch, povidone K29/32, stearic acid, microcrystalline cellulose, crospovidone (type A), anhydrous colloidal silica, brilliant blue, aluminium lake (E133), indigotine, aluminium lake (E132).
Tablet coating:
Polydextrose, titanium dioxide (E171), hypromellose (2910) (3cP, 6cP, 50cP), brilliant blue, aluminium lake (E133), triacetin, polyethylene glycol 400, 8000.

What Gripex DAY and NIGHT looks like and contents of the pack
Tablet (yellow) "for day"
Yellow, round coated tablets. Tablet dimensions are approximately 12 mm x 8 mm.
Tablet (blue) "for night"
Blue, round coated tablets. Tablet dimensions are approximately 12 mm x 6 mm.

Pack contents
PVC/PVDC/aluminium blister pack containing 6 yellow coated tablets "for day" and 2 blue coated tablets "for night" in a cardboard box.
Pack size:
16 coated tablets (2 blisters each containing 6 yellow tablets "for day" and 2 blue tablets "for night").

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
US Pharmacia Sp. z o.o.
ul. Ziębicka 40
50-507 Wrocław
Poland

Manufacturer
US Pharmacia Sp. z o.o.
ul. Ziębicka 40
50-507 Wrocław
Poland

For further information on this medicinal product, please contact:
USP Zdrowie Sp. z o.o.
ul. Poleczki 35
02-822 Warszawa
tel. +48 (22) 543 60 00

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Lithuania: Digrin 500 mg/30 mg/15 mg + 500 mg/30 mg/15 mg/2 mg plėvele dengtos tabletės
Poland: Gripex DAY and NIGHT