Fromilid

Package leaflet: Information for the patient

Fromilid, 125 mg/5 ml, granules for the preparation of oral suspension
Clarithromycinum
Please read carefully the entire leaflet 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 or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are identical.
• If you experience any adverse reactions, including any adverse reactions 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. What you need to know 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 exerts antibacterial action 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 children aged 6 months to 12 years.
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 heart rhythm disorders;
• if the patient is taking astemizole or terfenadine (medicines used for allergies), cisapride or domperidone (a medicine used for gastrointestinal motility disorders), pimozide (a medicine used for psychiatric disorders), because concomitant use with Fromilid may cause 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 (medicines from the statin group, 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 has, or has had in the past, heart rhythm disorders (ventricular arrhythmias, including torsade de pointes) or electrocardiogram (ECG) abnormalities known as "long QT syndrome", either in themselves 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, inform the doctor immediately:

• severe hypersensitivity reactions such as maculopapular rash, urticaria, petechiae, laryngeal oedema, or bronchospasm – immediate medical attention is required; appropriate treatment will be initiated by the doctor;
• 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 indicating liver dysfunction, such as loss of appetite, jaundice, dark urine, itching, or abdominal pain; discontinue treatment and consult a doctor immediately;
• new infection (superinfection) with bacteria resistant to clarithromycin or with 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 and other medicines
Inform the doctor about all medicines currently or recently taken, as well as any medicines the patient plans to take.
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);
• oral 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 oral mucosal 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 that reduces gastric acid secretion);
• cilostazol (a medicine used for intermittent claudication, characterised by pain in the lower limb muscles during exertion, subsiding after brief 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 for bronchial asthma);
• tolterodine (a medicine used for urinary incontinence);
• phenobarbital (an anticonvulsant);
• St John's wort ([Hypericum perforatum], a herbal medicine used for mild depression);
• sulfonylureas, nateglinide, repaglinide, insulin (medicines used for diabetes);
• ototoxic medicines, particularly aminoglycosides, e.g. gentamicin.

It is also important when taking medicines with the following names:

• hydroxychloroquine or chloroquine (used, among others, for rheumatoid arthritis, and for 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 the immune system, which is useful 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 a liquid after taking the medicine. The suspension contains granules which children should not chew, 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 become pregnant, she should consult a doctor or pharmacist before taking 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 foetus.
Since clarithromycin passes into human milk, women who are breastfeeding should exercise particular caution when taking 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
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 1.66 g of sucrose. The medicine contains 13.28 g of sucrose in the maximum daily dose. This should be taken into account in patients with diabetes.

3. How to take Fromilid

This medicine should always be taken exactly as directed by the physician. In case of doubts, consult
your doctor or pharmacist.
The dosage and duration of treatment depend on the type and location of infection, the patient's age, and
the individual response to treatment.
Recommended dosage in children and adolescents
The recommended daily dose of Fromilid suspension is 7.5 mg/kg body weight twice daily (see table – Children under 12 years of age), with a maximum dose in the treatment of infections not caused by mycobacteria of 500 mg twice daily.
The usual duration of treatment ranges from 5 to 10 days, depending on the causative microorganism and the course of the disease. The medicine may be taken during or between meals. Fromilid may be administered with milk.
Children under 12 years of age
The physician will determine the dosage of Fromilid according to the child's body weight.

*For children with body weight less than 8 kg, the dose should be calculated based on 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 with 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 a beneficial clinical effect is observed. It may be necessary to add other drugs active against Mycobacterium.
Instructions for preparing the suspension
To prepare 60 ml of suspension (125 mg/5 ml), always use boiled and cooled water.
First, invert the bottle and gently shake to disperse 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 until the powder is completely dispersed. Wait a moment, and after the foam has settled, slowly add water up to the mark on the bottle and shake vigorously again. The bottle must be shaken before each use.
After preparation, fine particles may be visible in the suspension, which is a normal phenomenon. The particles should not be chewed, as their contents have a bitter taste.
If after taking the medicine the patient feels particles in the mouth, the suspension may be followed by additional water.
5 ml of suspension measured with the dosing device supplied in the package contains 125 mg of clarithromycin.
Storage conditions for the suspension – see section 5: How to store Fromilid.
Taking more than the recommended dose of Fromilid
If more medicine is 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 administer appropriate symptomatic treatment.
As with other macrolide antibiotics, haemodialysis or peritoneal dialysis do not reduce serum concentrations of clarithromycin.
Missing a dose of Fromilid
If a dose is missed at the scheduled time, it should be taken as soon as possible.
However, if the time for 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. Stopping treatment too early may cause the disease to recur.
If there are any further doubts regarding the use of this medicine, consult a 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 of treatment,
stop taking Fromilid and consult a doctor immediately:

• anaphylactic shock – an acute, life-threatening allergic reaction, manifested, among others, by confusion, skin pallor, drop in 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, breathing difficulties
• 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, rapidly and spontaneously resolving 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, shedding of large sheets of epidermis, and fever
• DRESS syndrome – a severe (life-threatening) drug-induced reaction characterized by increased eosinophil count 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, 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:
The following common adverse reactions (may occur in 1 to 10 out of 100 patients) have been reported in clinical trials and following the marketing of clarithromycin:

• 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;
• balance disorders, hearing loss, tinnitus;
• palpitations, ECG changes (prolongation of QT interval);
• gastritis, stomatitis, glossitis, constipation, dry mouth, belching, flatulence;
• increased alanine aminotransferase (ALT) activity, increased aspartate aminotransferase (AST) activity;
• maculopapular rash;
• muscle cramps;
• fever, asthenia (weakness, lack of energy).

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

• rosacea;
• agranulocytosis (reduction in granulocyte count), thrombocytopenia (reduction in 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;
• tongue discoloration, tooth discoloration;
• 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 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 (AST) and alanine aminotransferase (ALT) activity, increased blood urea nitrogen, decreased platelet and white blood cell counts.

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 of 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicinal product.

5. How to store Fromilid

Keep the medicine out of the sight and reach of children.
Store the granulate for oral suspension preparation 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 stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the package and other information

What the medicine Fromilid contains

• The active substance is clarithromycin. 5 ml of the suspension contains 125 mg of clarithromycin.
• The other ingredients are: carbomer 934 P, povidone, hypromellose phthalate (HP55), talc, castor oil, xanthan gum, banana flavour, citric acid, potassium sorbate, colloidal anhydrous silica, titanium dioxide, sucrose. See section 2 “Fromilid contains sucrose”.

What Fromilid looks like and contents of the pack
The 125 mg/5 ml oral suspension granules are white to almost white, small, heterogeneous granules with a banana odour.
Pack sizes available: bottle containing 25 g of granules for the preparation of 60 ml of suspension, supplied with a 5 ml dosing applicator, 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 on this medicine, contact the local representative of the Marketing Authorisation Holder:
KRKA Polska Sp. z o.o.,
ul. Równoległa 5,
02-235 Warsaw,
Poland
tel.: (22) 57 37 500