Fromilid

Package leaflet: Information for the patient

Fromilid, 250 mg/5 ml, granules for oral suspension
Clarithromycinum
Please read the entire leaflet carefully before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, 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 the same.
• If you experience any adverse reactions, including any 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 called 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 many aerobic and anaerobic Gram-positive and Gram-negative bacteria.

Fromilid oral suspension is intended for adults and children over 12 years of age.
Clarithromycin in the form of oral suspension is indicated for the treatment of the following infections caused by microorganisms sensitive to clarithromycin:

• upper respiratory tract infections (e.g. streptococcal pharyngitis);
• acute otitis media;
• lower respiratory tract infections (e.g. bronchitis, pneumonia);
• skin and soft tissue infections (e.g. impetigo, folliculitis, cellulitis, abscesses);
• disseminated or localized infections caused by Mycobacterium avium or Mycobacterium intracellulare; localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum, or Mycobacterium kansasii.

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, for migraine) or oral midazolam (a medicine used for anxiety and insomnia);
• if the patient is taking medicines that may cause severe cardiac arrhythmias;
• if the patient is taking astemizole or terfenadine (medicines used for allergies), cisapride or domperidone (medicines used for gastrointestinal motility disorders), or pimozide (a medicine used for psychiatric disorders), because concomitant use with Fromilid may lead to severe cardiac arrhythmias;
• 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 or simvastatin (statin group medicines used to reduce blood cholesterol levels);
• if the patient is taking a medicine containing lomitapide;
• if the patient has severe hepatic insufficiency associated with renal insufficiency;
• if the patient has previously experienced cardiac arrhythmias (ventricular arrhythmias, including torsade de pointes) or ECG abnormalities (electrocardiogram) known as "long QT syndrome", either personally or in their family;
• 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 to the patient:

• 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 with other medicines".

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

• severe hypersensitivity reactions such as maculopapular rash, urticaria, petechiae, laryngeal oedema, or bronchospasm – the patient must immediately contact a doctor who will initiate appropriate treatment;
• diarrhoea, especially if acute or prolonged; the patient should 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, itching, or abdominal pain; treatment should be discontinued and the patient should consult a doctor;
• new infection (superinfection) caused by bacteria resistant to clarithromycin or by 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 show resistance to other macrolide antibiotics, as well as to lincomycin and clindamycin).

Fromilid with other medicines
Inform the doctor about all medicines currently used, recently used, 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, for migraine);
• astemizole or terfenadine (medicines used for allergies);
• cisapride or domperidone (medicines used for gastrointestinal motility disorders);
• pimozide (a medicine used for 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 for gout);
• statins – lovastatin, simvastatin (medicines that lower blood cholesterol levels);
• orally administered midazolam (a medicine used for anxiety or insomnia).

Inform the doctor if the patient is taking any of the following medicines, as special caution is required when using them concomitantly with Fromilid:

• rifampicin, rifapentine, rifabutin (antibiotics used in the treatment of tuberculosis);
• fluconazole, itraconazole (antifungal medicines);
• atazanavir, efavirenz, etravirine, nevirapine, ritonavir, saquinavir, zidovudine (used in the treatment of HIV infection);
• digoxin, quinidine, disopyramide, verapamil, amlodipine, diltiazem (used in the treatment of cardiac arrhythmias or hypertension);
• alprazolam, triazolam, intravenous or buccal midazolam (medicines used for 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 that resolves with short rest);
• cyclosporine, tacrolimus, sirolimus (medicines used, among others, after organ transplantation);
• sildenafil, tadalafil, vardenafil (medicines used for erectile dysfunction);
• ibrutinib or vinblastine (medicines used in cancer chemotherapy);
• theophylline (a medicine used in bronchial asthma);
• tolterodine (a medicine used for urinary incontinence);
• phenobarbital (an anticonvulsant medicine);
• St. John’s wort ([Hypericum perforatum], a herbal medicine used for mild depression);
• sulfonylureas, nateglinide, repaglinide, insulin (medicines used in diabetes);
• ototoxic medicines (damaging hearing), particularly aminoglycosides, e.g. gentamicin.

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). Concomitant use of these medicines with clarithromycin may increase the risk of cardiac arrhythmias and other serious adverse effects on the heart.
• corticosteroids administered orally, by injection, or by inhalation (used to suppress the immune system, which is beneficial in treating many different conditions).

Taking Fromilid with food and drink
Fromilid may be taken independently of meals. It is recommended that the patient drinks some fluid after taking the medicine. The oral suspension contains granules that should not be chewed by children, as their contents have a bitter taste.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine.
The safety of clarithromycin 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 fetus.
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. The patient should not drive or operate machinery if these symptoms occur.

Fromilid contains sucrose and sodium
If the patient has previously been diagnosed with an intolerance to certain sugars, they should consult a doctor before taking this medicine.
Each 5 ml of oral suspension contains 1.28 g of sucrose. The medicine contains 5.12 g of sucrose in the maximum daily dose. This should be taken into account in patients with diabetes.
The medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning the medicine is considered "sodium-free".

3. How to take Fromilid

This medicine should always be taken according to the doctor's instructions. If in doubt, consult
your doctor or pharmacist.
The dosage and duration of treatment depend on the type and location of infection, the patient's age,
and their response to treatment.
Recommended dosage for children and adolescents
The recommended daily dose of Fromilid suspension is 7.5 mg/kg body weight twice daily (see table – Dosage in children according to body weight), with a maximum dose in the treatment of infections not caused by mycobacteria of 500 mg twice daily.
The duration of treatment is usually from 5 to 10 days, depending on the type of pathogenic microorganism and the course of the disease. The medicine may be taken during or between meals. The medicine may be taken with milk.
The dosage of Fromilid will be determined by the doctor according to the child's body weight.

*For children with body weight less than 8 kg, the dose should be calculated according to body weight
(7.5 mg/kg body weight twice daily).
Dosing in patients with renal impairment
In patients with renal impairment, the dose of clarithromycin should be reduced by half, i.e. to 250 mg
once daily or, in the treatment of more severe infections, to 250 mg twice daily. In these patients, treatment
should not last longer than 14 days.
Dosing in patients with infections caused by Mycobacterium
In children, in cases of disseminated or localized infections caused by Mycobacterium
(M. avium, M. intracellulare, M. cheloneae, M. fortuitum, M. kansasii), the recommended daily dose of
clarithromycin is 15 to 30 mg/kg body weight, divided into two doses. The maximum dose is 500 mg
twice daily.
Treatment should be continued as long as beneficial clinical effects are observed. It may be necessary to
add other drugs active against Mycobacterium.
Instructions for preparing the suspension
To prepare 60 ml of suspension (250 mg/5 ml), always use boiled and cooled water.
First, invert the bottle and gently shake to loosen the powder. To prepare the suspension, fill the bottle
with water up to about halfway below the mark indicated on the bottle. Close the bottle and shake
vigorously until the powder is completely dispersed. Wait a moment for the foam to settle, then slowly
add water up to the mark on the bottle and shake again vigorously. The bottle should be shaken before
each use.
After preparation, small granules may be visible in the suspension, which is a normal phenomenon. The
granules should not be chewed, as their contents have a bitter taste.
If after taking the medicine the patient feels granules in the mouth, the suspension may be followed with
a glass of water.
5 ml of suspension measured with the dosing syringe supplied in the package contains 250 mg of
clarithromycin.
Storage conditions for the suspension – see section 5: How to store Fromilid.
Accidental overdose of Fromilid
If more medicine has been taken than recommended, contact a 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, haemodialysis or peritoneal dialysis do not significantly reduce
serum concentrations of clarithromycin.
Missed dose of Fromilid
If a dose has been missed at the scheduled time, it should be taken as soon as possible. However, if the
next dose is approaching, the missed dose should be skipped and the regular dosing schedule should be
continued.
A double dose should not be taken to make up for a missed dose.
Stopping treatment with Fromilid
Do not stop taking the medicine without consulting a doctor. Premature discontinuation of treatment
may result in recurrence of the disease.
If you have any further questions regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicinal product may cause adverse reactions, although not everyone experiences them.
If any of the following adverse reactions occur in a patient at any stage during treatment, discontinue the use of Fromilid and consult a doctor immediately:

• Anaphylactic shock – an acute, life-threatening allergic reaction, manifested, among others, by confusion, pale skin, drop in blood pressure, sweating, low urine output, rapid breathing, weakness, and fainting
• Allergic reactions: rash (common), itching, urticaria (not common), 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
• Erythema multiforme bullosum (Stevens-Johnson syndrome) characterized by sudden onset of fever and blisters, which resolve rapidly and spontaneously after discontinuation of the drug; a severe condition manifested by 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, shedding of large sheets of epidermis, and fever
• DRESS syndrome – a severe (life-threatening) drug-induced 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 completion of clarithromycin treatment. In such a case, contact a doctor immediately.
• Yellowing of the skin (jaundice), skin irritation, pale stool, dark urine, abdominal tenderness, or loss of appetite. These may be symptoms of liver failure.
• Severe upper abdominal pain, nausea, vomiting, diarrhoea, and fever. These may be symptoms of acute pancreatitis.

These reactions occur at an unknown frequency unless otherwise stated.
Other adverse reactions:
In clinical trials and following the marketing of clarithromycin, the following common adverse reactions have been reported (may occur in 1 to 10 out of 100 patients):

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

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

• Infection, candidiasis (fungal infection), vaginal infection;
• Decreased white blood cell count, increased platelet count;
• Anorexia, decreased appetite;
• Anxiety, nervousness;
• Dizziness, somnolence, tremor;
• Loss of balance, hearing loss, tinnitus;
• Palpitations, ECG changes (prolongation of QT interval);
• Gastritis, stomatitis, glossitis, constipation, dry mouth, belching, flatulence;
• Increased activity of hepatic alanine aminotransferase enzyme, increased activity of aspartate aminotransferase;
• Maculopapular rash;
• Muscle spasms;
• Fever, asthenia (weakness, lack of energy).

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

• Roseola;
• Agranulocytosis (reduced number of granulocytes in blood), thrombocytopenia (reduced number of platelets in blood);
• Acne;
• Psychotic disorder, confusion, depersonalization, depression, disorientation, hallucinations, abnormal dreams, mania;
• Seizures, loss of taste, parosmia, anosmia, paraesthesiae (numbness, tingling);
• Deafness;
• Torsade de pointes arrhythmia, ventricular tachycardia, ventricular fibrillation;
• Bleeding;
• Tongue discoloration, tooth discoloration;
• Myopathy (muscle disease with muscle weakness);
• Renal failure, interstitial nephritis;
• Changes in diagnostic test results (increased 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 adult patients with impaired immunity:

• Nausea, vomiting, taste disturbances, 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, decreased platelet and white blood cell count.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions 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
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.
Store the granules for oral suspension at a temperature not exceeding 30°C.
The prepared suspension is suitable for use for 14 days. Store the prepared suspension at a temperature not exceeding 25°C and protect from light.
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 specified month.
Medicines must 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 packaging and other information

What the medicine Fromilid contains

• The active substance is clarithromycin. 5 ml of the suspension contains 250 mg of clarithromycin.
• The other ingredients are: carbomer, povidone, hypromellose phthalate (HP55), talc, castor oil, xanthan gum, orange flavour, citric acid, potassium sorbate, colloidal anhydrous silica, titanium dioxide, sucrose, Sucram PH 280: sodium saccharin, ammonium glycyrrhizinate, neohesperidin dihydrochalcone. See section 2 "Fromilid contains sucrose and sodium".

What Fromilid looks like and contents of the pack
The 250 mg/5 ml oral suspension granules are white to almost white, small, non-uniform granules with an orange odour.
Pack sizes available: bottle containing 25 g of granules for the preparation of 60 ml of suspension, supplied with a 5 ml dosing syringe, packed in a cardboard box.

Marketing Authorisation Holder and Manufacturer
KRKA, d.d., Novo mesto,
Šmarješka cesta 6,
8501 Novo mesto,
Slovenia

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
KRKA - Polska Sp. z o.o.,
Równoległa Street 5,
02-235 Warsaw,
Poland
Tel.: (22) 57 37 500