Frobeflu

Package leaflet: Information for the patient

FROBEFLU

330 mg + 200 mg effervescent tablets
acetylsalicylic acid / ascorbic acid
Please read this leaflet carefully before taking this medicine as it contains
important information for you.

• Always take this medicine exactly as described in this leaflet or as your doctor or pharmacist has instructed.
• Keep this leaflet. You may need to read it again.
• If you need more information or advice, consult your pharmacist.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.
• Consult your doctor if you do not notice any improvement or if your symptoms worsen after three days of use at the maximum dose or after five days of use.

Contents of this leaflet:

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

1. What FROBEFLU is and what it is used for

FROBEFLU contains the active substances acetylsalicylic acid and ascorbic acid. Acetylsalicylic acid belongs to a group of medicines called non-steroidal anti-inflammatory drugs used to treat mild pain and inflammation. Ascorbic acid is a vitamin also known as vitamin C.
FROBEFLU is used to treat symptoms associated with fever and pain, such as influenza-like conditions, colds, headache, toothache, rheumatic and muscular pain, menstrual pain, and nerve pain (neuralgia).

Consult your doctor if you do not feel better or feel worse after three days of use at the maximum dose or after five days of use.

2. What you need to know before taking FROBEFLU

Do not take FROBEFLU

• if you are allergic to acetylsalicylic acid, ascorbic acid, or any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to medicines belonging to the group of salicylates or non-steroidal anti-inflammatory drugs (NSAIDs);
• if you have previously experienced stomach or intestinal bleeding or stomach lesions due to prior treatments;
• if you currently have stomach or duodenal lesions (ulcer) or suffer from other stomach diseases (gastropathies);
• if you have a tendency to bleed, for example, if you suffer from blood coagulation disorders (haemophilia, hypoprothrombinaemia, or vitamin K deficiency);
• if you suffer from severe heart problems (severe heart failure);
• if you suffer from severe kidney or liver problems (renal or hepatic insufficiency);
• if you suffer from bronchial asthma (narrowing of the lower airways leading to breathing difficulties), especially if you also have other respiratory problems (nasal polyps and angioedema);
• if you are under 16 years of age;
• if you are infected with varicella or influenza virus, as it may cause serious complications (Reye's syndrome), particularly in children and adolescents (see section “Children and adolescents”);
• at doses exceeding 100 mg per day during the third trimester of pregnancy (see section “Pregnancy, breastfeeding and fertility”);
• if you are breastfeeding;
• if you have a deficiency of a specific enzyme, glucose-6-phosphate dehydrogenase, which causes blood problems;
• if you are taking methotrexate (at doses of 15 mg/week or more) or warfarin (see “Other medicines and FROBEFLU”).

Warnings and precautions
Talk to your doctor or pharmacist before taking FROBEFLU.
Avoid taking FROBEFLU in combination with other NSAIDs (non-steroidal anti-inflammatory drugs), including selective COX-2 inhibitors such as celecoxib, valdecoxib, lumiracoxib, etc. (see “Other medicines and FROBEFLU”).
Avoid using high doses and/or for prolonged periods without first consulting your doctor and under his or her direct supervision.
Unwanted effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 3 “How to take FROBEFLU”).

Surgery
Do not take this medicine before undergoing surgery, as it may interfere with blood coagulation during surgical procedures (even minor ones, such as tooth extractions), potentially causing bleeding. Inform your surgeon about possible effects on blood coagulation if you have taken acetylsalicylic acid or another NSAID.
If you experience prolonged vomiting or profound drowsiness during treatment, stop taking the medicine immediately.

Use particular caution in the following cases:

• if you are elderly and have kidney problems or low levels of the blood protein albumin, as the medicine may be toxic in such cases;
• if you suffer from chronic or recurrent gastrointestinal disorders (ulcerative colitis, Crohn’s disease), as these conditions may worsen;
• if you are taking medicines used to improve blood coagulation (anticoagulants or antiplatelet agents), medicines for anxiety and depression (selective serotonin reuptake inhibitors), or anti-inflammatory medicines (corticosteroids), as there is a risk of bleeding (haemorrhage) (see section “Other medicines and FROBEFLU”);
• if you suffer from or have suffered from kidney stones;
• if you suffer from blood disorders such as haemochromatosis, thalassaemia, or sideroblastic anaemia;
• if you suffer from high blood pressure or heart problems (heart failure), as fluid retention (tendency to retain fluids in the body) and oedema (fluid accumulation in tissues) have been reported in association with NSAID therapy. The risk is higher in patients treated with diuretics;
• if you are taking medicines used to increase urine production (spironolactone, furosemide) or medicines for gout treatment, unless otherwise directed by your doctor, as their effectiveness may be reduced by this medicine (see section “Other medicines and FROBEFLU”).

It is advisable to consult your doctor if you have:

• gastrointestinal disorders;
• reduced kidney function (mild to moderate decrease in kidney function);
• any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly in the early stages of treatment;
• if you are in the first or second trimester of pregnancy (see “Pregnancy, breastfeeding and fertility”);
• if you are diabetic, as salicylates may enhance the hypoglycaemic effect of sulphonylureas.

During treatment with all non-steroidal anti-inflammatory drugs (NSAIDs), gastrointestinal bleeding, ulceration, and perforation—some of which may be fatal—have been reported at any time, with or without warning symptoms or history of serious gastrointestinal events.
The risk of gastrointestinal bleeding, ulceration, or perforation is higher with high NSAID doses in patients who have previously experienced ulcer episodes, especially if complicated by bleeding or perforation (see section 4 “Possible side effects”). Individuals who habitually consume large amounts of alcohol are at increased risk of bleeding.
In such cases, treatment should be initiated at the lowest available dose, and concomitant use of gastroprotective agents (e.g., misoprostol or proton pump inhibitors) should be considered. The use of gastroprotective agents should also be considered when taking low-dose acetylsalicylic acid or other medicines that may increase the risk of gastrointestinal events (see “Other medicines and FROBEFLU”).
If gastrointestinal bleeding or ulceration occurs while taking FROBEFLU,
stop treatment immediately and do not resume without first consulting your doctor.
Very rare but serious skin reactions, some of which have been fatal (exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis), have been reported with NSAID use (see section 4). These reactions typically occur within the first month of treatment. Stop taking FROBEFLU and consult your doctor or pharmacist if you notice a skin rash, mucosal lesions, or any other signs of hypersensitivity.
Acetylsalicylic acid and other NSAIDs may cause allergic reactions including asthma attacks, runny nose, angioedema (swelling of the skin, face, and mucous membranes), or urticaria (small itchy skin patches).
Reactions may be more frequent and severe in individuals with asthma and/or rhinitis (with or without nasal polyps) and/or urticaria.
Acetylsalicylic acid affects uric acid levels in the blood (uricaemia).
Metrorrhagia or menorrhagia: concomitant use of acetylsalicylic acid may increase the risk of increased intensity and duration of bleeding.

Children and adolescents
This medicine is contraindicated in children and adolescents under 16 years of age (see section “Do not take FROBEFLU”), especially if they have viral infections such as influenza A, influenza B, or varicella. In such cases, there is a risk of a very rare but life-threatening condition called Reye’s syndrome, which requires immediate medical attention and is characterized by persistent vomiting and damage to the central nervous system (lethargy, generalized seizures, and coma), liver injury, and low blood sugar levels (hypoglycaemia).

Elderly
Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforations, which may be fatal (see section 3 “How to take FROBEFLU”). The risk is higher with increased NSAID doses; therefore, these patients should start treatment with the lowest available dose, and concomitant use of gastroprotective agents (e.g., misoprostol or proton pump inhibitors) should be considered.
Patients over 70 years of age, especially those undergoing other treatments, should take this medicine only after consulting their doctor.

Other medicines and FROBEFLU
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Do not take FROBEFLU together with the following medicines (see “Do not take FROBEFLU”):

• Methotrexate (used in certain cancers and rheumatoid arthritis) (doses ≥15 mg/week);
• Warfarin (anticoagulant).

Take FROBEFLU with caution together with the following medicines:

• medicines for blood coagulation disorders (anticoagulants) and heparin;
• methotrexate, a medicine used to treat certain cancers, as acetylsalicylic acid increases its toxicity (at doses <15 mg/week);
• medicines used for inflammation (corticosteroids), blood thinning (antiplatelets), or anxiety and depression (selective serotonin reuptake inhibitors), as gastrointestinal bleeding may occur;
• other non-steroidal anti-inflammatory drugs, as they may increase unwanted effects;
• anagrelide, a drug used to reduce excessively high platelet levels, which may increase the risk of bleeding;
• antidiabetics: medicines that lower blood sugar levels, such as oral hypoglycaemics (sulphonylureas);
• diuretics (medicines to increase urine output) and antihypertensives: such as spironolactone, furosemide, and preparations used for gout;
• valproic acid: acetylsalicylic acid reduces the binding of valproic acid to serum albumin, increasing its plasma concentrations;
• pemetrexed, a medicine used in cancer treatment;
• metamizole (a substance used to reduce pain and fever), which may reduce the effect of acetylsalicylic acid on platelet aggregation (blood cells that clump together to form a clot) when taken simultaneously. Therefore, this combination should be used with caution in patients taking low-dose aspirin for cardioprotection;
• urinary alkalinizers (e.g., antacids, citrates): reduce the absorption of the medicine;
• digoxin and lithium: acetylsalicylic acid reduces renal excretion of digoxin and lithium, leading to increased plasma concentrations;
• carbonic anhydrase inhibitors (acetazolamide): reduced elimination of acetazolamide may cause severe acidosis and increased central nervous system toxicity;
• phenytoin: increased effect of phenytoin;
• metoclopramide and domperidone: increased effect of acetylsalicylic acid due to faster absorption;
• uricosurics (e.g., probenecid, benzbromarone, sulfinpyrazone): reduced uricosuric effect;
• varicella vaccine: salicylates should not be administered to patients who have received the varicella vaccine for a period of six weeks after vaccination. Cases of Reye’s syndrome have occurred following salicylate use during varicella infection;
• zafirlukast, an asthma medication whose blood concentration may increase;
• alcohol: increased risk of intestinal bleeding.

Discontinue treatment with this medicine several days before undergoing diagnostic tests, as vitamin C, especially at high doses, may interfere with test results, particularly non-specific glucose testing in urine.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
If you need to continue or start treatment with FROBEFLU during pregnancy as advised by your doctor, use FROBEFLU as directed and do not exceed the recommended dose.

Pregnancy – third trimester
Do not take FROBEFLU at doses exceeding 100 mg per day during the last three months of pregnancy, as it may harm the fetus or cause delivery complications. It may cause kidney and heart problems in the fetus. It may affect your and your baby’s tendency to bleed and may delay or prolong labour beyond expected duration.
If you take FROBEFLU at low doses (up to 100 mg per day inclusive), close obstetric monitoring as advised by your doctor is required.

Pregnancy – first and second trimesters
You should not take FROBEFLU during the first six months of pregnancy unless absolutely necessary and under medical advice. If treatment is required during this period or during attempts to conceive, the lowest possible dose for the shortest possible time should be used.
From week 20 of pregnancy, FROBEFLU may cause kidney problems in the fetus if taken for more than a few days, thereby reducing amniotic fluid levels surrounding the baby (oligohydramnios) or causing narrowing of a blood vessel (ductus arteriosus) in the baby’s heart. If treatment is needed for more than a few days, your doctor may recommend additional monitoring.

Breastfeeding
Acetylsalicylic acid passes into breast milk in small amounts: FROBEFLU must not be taken during breastfeeding.

Fertility
If acetylsalicylic acid is used by a woman trying to conceive, the dose and duration of treatment should be kept as low as possible.

Driving and using machines
This medicine, especially when taken at high doses, may cause headache or dizziness. If this occurs, avoid driving or operating machinery.

FROBEFLU contains sodium
The maximum recommended daily dose of this medicine contains 2908 mg of sodium (present in table salt). This corresponds to 145% of the recommended maximum daily sodium intake.
Talk to your doctor or pharmacist if you need to take 1 or more tablets daily for a prolonged period, especially if you have been advised to follow a low-sodium diet.

FROBEFLU contains sodium benzoate
This medicine contains 48 mg of sodium benzoate per tablet.

3. How to take FROBEFLU

Take this medicine exactly as described in this leaflet or as directed by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist.
The recommended dose for reducing fever and relieving mild to moderate pain is 1 tablet every 4-6 hours, as needed.
The recommended dose for rheumatic, muscular, and nerve pain is 1-2 tablets, 2 or 3 times daily.
Do not exceed the recommended doses without consulting your doctor.
Consult your doctor if you do not notice any improvement or if your symptoms worsen after three days of treatment at the maximum dose or after five consecutive days of FROBEFLU use.
Dissolve the tablets in a glass of water.
Take this medicine with food.

Elderly
It is recommended to take the lowest possible dosage.

If you take more FROBEFLU than you should
In case of accidental ingestion or overdose of FROBEFLU, contact your doctor immediately or go to the nearest hospital.
Salicylate toxicity (a dosage exceeding 100 mg/kg/day for two consecutive days may induce toxicity) can result from chronic intake of excessive doses or from acute overdose, which may be potentially life-threatening and may also include accidental ingestion in children.

Mild poisoning: Tinnitus (ringing in the ears), reduced hearing acuity, headache, and dizziness are characteristic signs of excessive dosing and can be managed by reducing the dose.

Severe poisoning: Symptoms include fever, hyperventilation (excessively deep breathing), ketosis (acetone), respiratory alkalosis (acid-base imbalance due to altered respiration), metabolic acidosis (accumulation of acidic molecules in the body), coma, cardiovascular collapse, respiratory failure, and severe hypoglycemia (decreased blood glucose concentration).

In such cases, the following supportive measures are required to limit drug absorption in the gastrointestinal tract:

• gastric lavage (forced emptying of the stomach);
• administration of activated charcoal (a substance that adsorbs excess drug on its surface);
• monitoring and correction of acid-base balance;
• alkaline diuresis (alkalinization of urine);
• correction of dehydration (excessive fluid loss) with adequate fluid administration;
• symptomatic supportive treatment.

If you forget to take FROBEFLU
If you forget to take a dose, take the next dose at the scheduled time. Do not take a double dose to make up for the missed dose.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
The following side effects may occur:

• stomach disorders (heartburn, epigastric pain), gastritis, constipation, nausea, vomiting, diarrhoea, excessive intestinal gas (flatulence), digestive disturbances (dyspepsia), abdominal pain, erosion of the oral mucosa (ulcerative stomatitis), worsening of previous gastrointestinal diseases (colitis, Crohn's disease, peptic ulcer, including perforated ulcer)
• gastrointestinal bleeding, sometimes fatal, which may present as vomiting or melena (dark stools due to presence of blood) or may be occult and cause iron-deficiency anaemia (reduced red blood cells due to iron deficiency). Such bleeding is more frequent with increasing dosage and in elderly patients. Less frequently, gastritis (inflammation of the mucosa lining the stomach) has been observed
• heart disorders (oedema, hypertension, heart failure)
• blistering skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• haemorrhagic syndromes such as nosebleeds (epistaxis), gingival haemorrhage, reduced platelet count in the blood (thrombocytopenia), purpura (small subcutaneous haemorrhages). This effect persists for 4–8 days after discontinuation of acetylsalicylic acid administration
• high doses of Vitamin C (> 1 g) may increase white blood cell breakdown (haemolysis) in patients with G6PD-dehydrogenase deficiency
• allergic reactions such as skin rashes, laryngeal swelling due to fluid accumulation, bronchial obstruction (bronchospasm), Quincke's oedema (swelling of large areas of the face and oral mucosa, which may also affect the respiratory and gastrointestinal systems), acute and non-acute asthma, nasal problems (nasal polyps), runny nose (rhinorrhoea), sudden swelling of the skin and mucous membranes (angioedema)
• ringing in the ears (tinnitus) and hearing loss, which may occur at high doses. In such cases, you must temporarily stop treatment or reduce the dosage
• reduced blood flow to the kidneys and worsening of kidney disorders (acute renal failure) in individuals who already suffer from such conditions
• high doses of Vitamin C (> 1 g) may promote the formation of kidney stones (oxalate and uric acid stones) in some individuals
• severe, rare, potentially fatal illness (Reye's syndrome)
• headache, dizziness
• rhinitis (runny nose), dyspnoea (difficulty breathing)
• bronchospasm (abnormal contraction of the smooth muscle of the bronchi or bronchioles), asthma attacks
• delayed labour.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store FROBEFLU

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp". The expiry date refers to the last day of that month.
Store in a tightly closed container and at a temperature not exceeding 25°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What FROBEFLU contains
The active substances are acetylsalicylic acid and ascorbic acid. Each effervescent tablet contains
330 mg of acetylsalicylic acid and 200 mg of ascorbic acid.
The other components are: sodium bicarbonate, anhydrous citric acid, glycine, sodium benzoate (E211).
Description of the appearance of FROBEFLU and pack contents
Pack containing 10 or 20 effervescent tablets.
Marketing Authorization Holder
Cooper Consumer Health B.V.
Verrijn Stuartweg 60 – 1112 AX Diemen
(The Netherlands)
Manufacturer
E-Pharma Trento S.p.A., Via Provina 2, Frazione Ravina, 38123 – Trento (TN)
Special Product’s Line S.p.A., via Fratta Rotonda vado Largo, 1, 03012 Anagni (FR)