Fromilid 250

Patient Information Leaflet

Fromilid 250, 250 mg, coated tablets
Fromilid 500, 500 mg, coated tablets
Clarithromycinum
Please read this leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else even if their symptoms are identical.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents

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

1. What Fromilid is and what it is used for

Fromilid belongs to a group of antibiotics known as macrolides with broad-spectrum antibacterial activity. Clarithromycin, the active substance in Fromilid, is a derivative of erythromycin and exhibits antibacterial activity against both standard bacterial strains and strains isolated from patients. Clarithromycin is active against numerous aerobic and anaerobic Gram-positive and Gram-negative bacteria.

Clarithromycin in tablet form is indicated for the treatment of the following infections caused by microorganisms sensitive to clarithromycin:

• Tonsillitis and pharyngitis;
• Acute maxillary sinusitis;
• Otitis media;
• Exacerbation of chronic bronchitis;
• Pneumonia;
• Uncomplicated skin and soft tissue infections;
• Disseminated mycobacterial infections.

Fromilid is also used for eradication of Helicobacter pylori in patients with duodenal or gastric ulcer. In this indication, your doctor will prescribe Fromilid together with agents that inhibit gastric acid secretion and another antibiotic.

2. Important information before taking Fromilid

When not to take Fromilid

• if the patient is allergic to clarithromycin, other macrolide antibiotics (such as azithromycin, erythromycin), or any of the other ingredients of this medicine (listed in section 6);
• if the patient is taking ergot alkaloids, such as ergotamine or dihydroergotamine (medicines used, among others, in migraine), or oral midazolam (a medicine used in anxiety and insomnia);
• if the patient is taking medicines that may cause severe heart rhythm disorders;
• if the patient is taking astemizole or terfenadine (medicines used in allergy), cisapride or domperidone (medicines used in gastrointestinal motility disorders), pimozide (a medicine used in psychiatric disorders), because concomitant use with Fromilid may lead to severe heart rhythm disturbances;
• if the patient is taking ticagrelor (a platelet aggregation inhibitor), ivabradine or ranolazine (medicines used in the treatment of angina pectoris);
• if the patient has low blood potassium or magnesium levels (hypokalaemia or hypomagnesaemia);
• if the patient is taking lovastatin, simvastatin (statins, medicines used to reduce blood cholesterol levels);
• if the patient is taking a medicine containing lomitapide;
• if the patient has severe hepatic insufficiency with concomitant renal insufficiency;
• if the patient or a family member has previously experienced heart rhythm disorders (ventricular arrhythmias, including torsade de pointes) or electrocardiogram (ECG) abnormalities known as "long QT syndrome";
• if the patient is taking colchicine (a medicine used in the treatment of gout).

Warnings and precautions
Before starting treatment with Fromilid, consult a doctor if any of the following apply:

• the patient is pregnant or suspects she may be pregnant,
• the patient has impaired kidney or liver function,
• the patient has coronary artery disease, severe heart failure, or bradycardia (slow heart rate),
• the patient is taking any of the medicines listed in the section "Fromilid and other medicines".

If any of the following occur during treatment with Fromilid, inform the doctor immediately:

• severe hypersensitivity reactions, such as maculopapular rash, urticaria, petechiae, laryngeal oedema, bronchospasm – immediate medical attention is required;
• diarrhoea, especially if acute or prolonged; inform the doctor as soon as possible. If necessary, the doctor will recommend appropriate treatment; do not use anti-diarrhoeal medicines;
• symptoms suggesting liver dysfunction, such as loss of appetite, jaundice, dark urine, pruritus, or abdominal pain; discontinue treatment and consult a doctor;
• new infection (superinfection) with bacteria resistant to clarithromycin or fungi, particularly during prolonged antibiotic use – the doctor will recommend appropriate treatment.

Additionally, during treatment with Fromilid the following may occur:

• bacterial cross-resistance (bacteria resistant to clarithromycin may also be resistant to other macrolide antibiotics, as well as to lincomycin and clindamycin),
• bacterial antibiotic resistance (e.g. treatment of Helicobacter pylori infection may lead to emergence of resistant microorganisms).

If symptoms indicating damage to the hearing organ or vestibular system occur (see section 4), appropriate follow-up examinations are recommended after completion of treatment.

Fromilid and other medicines
Inform the doctor about all medicines currently used, recently taken, or planned for use.

It is essential to inform the doctor if the patient is taking any of the following medicines, as their concomitant use with Fromilid is contraindicated:

• ergot alkaloids, such as ergotamine or dihydroergotamine (medicines used, among others, in migraine);
• astemizole or terfenadine (medicines used in allergy);
• cisapride or domperidone (medicines used in gastrointestinal motility disorders);
• pimozide (a medicine used in psychiatric disorders);
• ticagrelor, ivabradine, ranolazine (medicines used in the treatment of angina pectoris or to reduce the risk of myocardial infarction or stroke);
• colchicine (a medicine used in gout);
• statins – lovastatin, simvastatin (medicines lowering blood cholesterol levels);
• oral midazolam (a medicine used in anxiety or insomnia).

Inform the doctor if the patient is taking any of the following medicines, as special caution is required during concomitant use with Fromilid:

• rifampicin, rifapentine, rifabutin (antibiotics used in tuberculosis treatment);
• fluconazole, itraconazole (antifungal medicines);
• atazanavir, efavirenz, etravirine, nevirapine, ritonavir, saquinavir, zidovudine (used in HIV infection treatment);
• digoxin, quinidine, disopyramide, verapamil, amlodipine, diltiazem (used in heart rhythm disorders or hypertension);
• alprazolam, triazolam, intravenous or oral mucosal midazolam (medicines used in anxiety or insomnia);
• warfarin or any other anticoagulant, e.g. dabigatran, rivaroxaban, apixaban, edoxaban (medicines used to thin the blood);
• quetiapine or other atypical antipsychotics;
• carbamazepine, valproate, phenytoin (antiepileptic medicines);
• methylprednisolone (an anti-inflammatory medicine);
• omeprazole (a medicine reducing gastric acid secretion);
• cilostazol (a medicine used in intermittent claudication, characterised by leg muscle pain during exertion, resolving after brief rest);
• cyclosporine, tacrolimus, sirolimus (medicines used, among others, after organ transplantation);
• sildenafil, tadalafil, vardenafil (medicines used in erectile dysfunction);
• ibrutinib or vinblastine (medicines used in cancer chemotherapy);
• theophylline (a medicine used in bronchial asthma);
• tolterodine (a medicine used in urinary incontinence);
• phenobarbital (an anticonvulsant medicine);
• St. John’s wort ([Hypericum perforatum], a herbal medicine used in mild depression);
• sulfonylureas, nateglinide, repaglinide, insulin (medicines used in diabetes);
• ototoxic medicines (damaging hearing), particularly aminoglycoside antibiotics used in bacterial infections.

This is also important when using medicines with the following names:

• hydroxychloroquine or chloroquine (used, among others, in the treatment of rheumatoid arthritis, and in the treatment or prevention of malaria). Taking these medicines together with clarithromycin may increase the risk of heart rhythm disturbances and other serious adverse effects on the heart.

• corticosteroids administered orally, by injection, or by inhalation (used to suppress immune system activity, useful in treating many different conditions).

Taking Fromilid with food and drink
Fromilid can be taken independently of meals. Do not divide the tablets. Swallow the tablets whole with liquid.

Pregnancy and breastfeeding
If the patient is pregnant, suspects she may be pregnant, is breastfeeding, or plans to become pregnant, she should consult a doctor or pharmacist before using this medicine.
The safety of clarithromycin use during pregnancy and breastfeeding has not been established. Fromilid may be used in pregnant women only if, in the opinion of the doctor, the benefit to the mother outweighs the potential risk to the foetus.
Since clarithromycin passes into human milk, women who are breastfeeding should exercise particular caution when using Fromilid.

Driving and operating machinery
Fromilid may cause dizziness, confusion, and disorientation, which may affect the ability to drive or operate machinery. Patients should not drive or operate machinery if these symptoms occur.

3. How to take Fromilid

This medicine should always be taken according to the doctor's instructions. If in doubt, consult a
doctor or pharmacist.
Do not divide the tablets. Swallow the tablets whole with liquid.
The dosage and duration of treatment depend on the type and location of infection, the patient's age,
and their response to treatment.
Recommended dose
Adults and adolescents over 12 years of age
The usual recommended dose is 250 mg every 12 hours.
Children under 12 years of age
Clinical trials involving children aged 6 months to 12 years have been conducted using clarithromycin
in the form of an oral suspension. Therefore, in children, clarithromycin oral suspension is recommended.
For the treatment of sinusitis, more severe infections, or infections caused by Haemophilus influenzae,
500 mg every 12 hours should be administered.
Treatment usually lasts from 6 to 14 days.
When using clarithromycin to eradicate H. pylori in patients with peptic ulcer disease, the daily dose
ranges from 500 to 1000 mg. Clarithromycin is usually administered in two divided doses over
7–14 days. Eradication of H. pylori requires concomitant administration of other medications.
Patients with renal impairment
In patients with renal impairment, the clarithromycin dose should be reduced by half, i.e.,
250 mg once daily, or in severe infections, 250 mg twice daily. The drug should not be administered
for longer than 14 days.
Taking more Fromilid than recommended
If you take more medicine than recommended, contact your doctor or pharmacist immediately.
Overdose may cause gastrointestinal disturbances (nausea, vomiting, abdominal pain). In case of
overdose, the doctor will provide appropriate symptomatic treatment.
As with other macrolide antibiotics, hemodialysis or peritoneal dialysis does not reduce serum
clarithromycin concentrations.
Missing a dose of Fromilid
If you miss a dose at the scheduled time, take it as soon as possible. However, if it is almost time
for the next dose, skip the missed dose and continue with your regular dosing schedule.
Do not take a double dose to make up for a missed dose.
Stopping the use of Fromilid
Do not stop taking this medicine without consulting your doctor. Stopping treatment too early may
cause the illness to return.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the following adverse reactions occur in a patient at any stage during treatment, stop taking Fromilid and consult a doctor immediately:

• Anaphylactic shock – an acute, life-threatening allergic reaction characterized, among others, by confusion, pale skin, low blood pressure, sweating, reduced urine output, rapid breathing, weakness, and fainting

• Allergic reactions: rash (common), itching, urticaria (uncommon), angioedema of the face, tongue, lips, eyes, and throat, difficulty breathing

• Severe skin reactions:

• Acute generalized exanthematous pustulosis – red, peeling rash with subcutaneous nodules and blisters

• Bullous erythema multiforme (Stevens-Johnson syndrome) characterized by sudden onset of fever and blisters, which resolve quickly and spontaneously after discontinuation of the drug; a severe condition presenting with blisters and erosions on the skin, in the oral cavity, eyes, and genital organs, accompanied by fever and joint pain

• Toxic epidermal necrolysis (Lyell's syndrome) – a severe, rapidly progressing disease characterized by rupturing giant subepidermal blisters, extensive skin erosions, large-scale peeling of the epidermis, and fever

• DRESS syndrome – a severe (life-threatening) drug reaction characterized by increased number of eosinophils and internal organ involvement

• Severe or prolonged diarrhoea, possibly with blood or mucus in the stool (pseudomembranous colitis). Diarrhoea may occur even up to two months after completing clarithromycin treatment. In such cases, contact a doctor immediately.

• Yellowing of the skin (jaundice), skin irritation, pale-coloured stools, dark-coloured urine, abdominal tenderness on palpation, or loss of appetite. These may be symptoms of liver failure, cholestasis (increased concentration of bile components in the blood), or hepatitis (uncommon). These reactions occur with unknown frequency unless otherwise stated.

Other adverse reactions:
The following common adverse reactions have been reported in clinical trials and following the marketing of clarithromycin:

• Insomnia;
• Taste disturbances, headache;
• Diarrhoea, vomiting, indigestion, nausea, abdominal pain;
• Abnormal liver function test results;
• Excessive sweating.

Uncommon adverse reactions (may occur in 1 to 10 out of 1,000 patients):

• Candidiasis (fungal infection), vaginal infection;
• Decreased white blood cell count, decreased neutrophil count, and increased eosinophil count;
• Anorexia, decreased appetite;
• Restlessness;
• Dizziness, drowsiness, tremor;
• Loss of balance, hearing loss, tinnitus;
• Palpitations, changes in ECG (prolongation of QT interval);
• Gastritis, oral inflammation, glossitis, abdominal distension, constipation, dry mouth, belching, flatulence;
• Increased liver enzyme activity: alanine aminotransferase, increased aspartate aminotransferase activity, increased gamma-glutamyltransferase activity;
• Malaise, asthenia (weakness, lack of energy), chest pain, chills, fatigue;
• Increased blood levels of alkaline phosphatase and lactate dehydrogenase enzymes.

The following adverse reactions have been reported after the marketing of clarithromycin tablets and suspension, with unknown frequency (frequency cannot be estimated from available data):

• Rosacea;
• Agranulocytosis (reduced granulocyte count in blood), thrombocytopenia (reduced platelet count);
• Acne;
• Psychotic disorder, confusion, depersonalization, depression, disorientation, hallucinations, unusual dreams, mania;
• Seizures, ageusia (loss of taste), parosmia (distorted sense of smell), anosmia (loss of smell), paresthesia (numbness, tingling);
• Deafness;
• Cardiac arrhythmias such as torsade de pointes, ventricular tachycardia, ventricular fibrillation;
• Bleeding;
• Acute pancreatitis, tongue discoloration, tooth discoloration;
• Liver failure, parenchymal jaundice;
• Myopathy (muscle disease with muscle weakness);
• Renal failure, interstitial nephritis;
• Changes in diagnostic test results (elevated international normalized ratio (INR), prolonged prothrombin time, abnormal urine color).

Patients with impaired immunity
In addition to symptoms related to the underlying disease, the following adverse reactions have been observed in immunocompromised adult patients:

• Nausea, vomiting, altered taste perception, constipation, abdominal pain, diarrhoea, flatulence, dry mouth;
• Headache, hearing disturbances;
• Rash;
• Dyspnoea, insomnia;
• Abnormal laboratory test results: increased aspartate aminotransferase (AspAT) and alanine aminotransferase (AlAT) activity, increased blood urea nitrogen levels, decreased platelet and white blood cell counts.

Reporting of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the 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
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 Fromilid

Keep this medicine out of sight and reach of children.
No special precautions for storage are required.
Do not use this medicine after the expiry date stated on the packaging after: EXP.
The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What the medicine Fromilid contains

• The active substance is clarithromycin. Each coated tablet contains 250 mg or 500 mg of clarithromycin.
• The other ingredients are: maize starch, microcrystalline cellulose, anhydrous colloidal silicon dioxide, pregelatinized starch, potassium polyacrylate, talc, magnesium stearate.
• Film-coating ingredients: hypromellose 6 cps, talc, iron oxide, yellow (E 172), propylene glycol, titanium dioxide (E 171).

What Fromilid looks like and contents of the pack
Oval, slightly biconvex, brownish-yellow coated tablet.
The pack contains film-coated tablets in blisters made of PVC/PVDC/Aluminium foil, packed in a cardboard box.
Fromilid 250
10 film-coated tablets (1 blister containing 10 tablets)
14 film-coated tablets (2 blisters containing 7 tablets each)
Fromilid 500
14 film-coated tablets (2 blisters containing 7 tablets each)
28 film-coated tablets (4 blisters containing 7 tablets each)
Marketing Authorisation Holder and Manufacturer
KRKA, d.d., Novo mesto,
Šmarješka cesta 6,
8501 Novo mesto,
Slovenia
For further information regarding this medicine, please contact the local representative of the Marketing Authorisation Holder:
KRKA-Polska Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
Poland
tel.: (22) 57 37 500