Klarmin

Package leaflet: Information for the patient

Klarmin, 500 mg, coated tablets
Clarithromycinum
Please read carefully the entire leaflet before taking the 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 doubts, please consult your doctor or pharmacist.
• 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 or pharmacist. See section 4.

Table of contents

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

1. What Klarmin is and what it is used for

Klarmin contains the active substance clarithromycin. It is a macrolide antibiotic which inhibits the growth of bacteria causing infections.
Klarmin is indicated for the treatment of infections caused by microorganisms sensitive to clarithromycin. These infections include:

• upper respiratory tract infections, e.g. streptococcal pharyngitis, sinusitis,
• lower respiratory tract infections, e.g. bronchitis, pneumonia,
• acute otitis media,
• skin and soft tissue infections, e.g. impetigo, folliculitis,
• connective tissue infections,
• disseminated or localized infections caused by mycobacteria.

In patients infected with HIV (CD4 lymphocyte count ≤ 100/mm³), Klarmin is indicated for the prevention of disseminated infections caused by the Mycobacterium avium complex (MAC).
In patients with duodenal ulcer and confirmed Helicobacter pylori infection, Klarmin should be used in combination with drugs that inhibit gastric acid secretion and another antibiotic.

2. Important information before using Klarmin

When not to use Klarmin

• If the patient is allergic to clarithromycin or other macrolide antibiotics (such as azithromycin, erythromycin) or to any of the other ingredients of this medicine (listed in section 6).
• If the patient is taking any of the following medicines:
• astemizole or terfenadine (medicines used to treat allergies), cisapride (a medicine used for gastrointestinal motility disorders), pimozide (a medicine used for psychiatric disorders) – because this may lead to severe cardiac arrhythmias,
• any other medicines known to cause cardiac arrhythmias,
• ticagrelor, ivabradine or ranolazine (medicines used to treat angina pectoris or to reduce the risk of heart attack or stroke),
• ergot alkaloids, such as ergotamine or dihydroergotamine (medicines used, among others, for migraine treatment),
• lovastatin, simvastatin (statins, medicines used to reduce blood cholesterol levels),
• midazolam administered orally (a medicine used for anxiety and insomnia),
• colchicine (a medicine used for gout treatment).
• If the patient has low blood potassium or magnesium levels (hypokalaemia or hypomagnesaemia).
• If the patient or a family member has previously been diagnosed with ECG abnormalities (prolonged QT interval) or cardiac arrhythmias (ventricular arrhythmias, including torsade de pointes).
• If the patient has severe hepatic insufficiency associated with renal insufficiency.
• If the patient is taking a medicine containing lomitapide.

Warnings and precautions
Before starting treatment with Klarmin, discuss with your doctor if:

• the patient is pregnant or suspects she may be pregnant,
• the patient has renal or hepatic impairment,
• the patient has coronary artery disease, severe heart failure, or bradycardia,
• the patient is taking any of the medicines listed in the section "Klarmin with other medicines".

If any of the following situations occur during treatment with Klarmin, inform the doctor immediately (see also section 4):

• severe hypersensitivity reactions such as maculopapular rash, urticaria, petechiae, laryngeal oedema, bronchospasm – immediately contact the doctor, who will initiate appropriate treatment;
• diarrhoea, especially severe 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 immediately contact the doctor;
• new infection (superinfection) with bacteria resistant to clarithromycin or with fungi, especially during prolonged antibiotic use – the doctor will recommend appropriate treatment.

Additionally, during treatment with Klarmin the following may occur:

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

Klarmin with other medicines
Inform your 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 use with Klarmin is contraindicated:

• astemizole or terfenadine (medicines used to treat allergies),
• cisapride (a medicine used for gastrointestinal motility disorders),
• pimozide (a medicine used for psychiatric disorders),
• ergot alkaloids, such as ergotamine or dihydroergotamine (medicines used, among others, for migraine treatment),
• statins – lovastatin, simvastatin (medicines lowering blood cholesterol levels),
• midazolam administered orally (a medicine used for anxiety or insomnia),
• colchicine (a medicine used for gout treatment).

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

• rifampicin, rifapentine, rifabutin (antibiotics used to treat tuberculosis),
• fluconazole, itraconazole (medicines used to treat fungal infections),
• atazanavir, efavirenz, etravirine, nevirapine, ritonavir, saquinavir, zidovudine (medicines used to treat HIV infection),
• digoxin, quinidine, disopyramide, verapamil, amlodipine, diltiazem (medicines used to treat cardiac arrhythmias or hypertension),
• alprazolam, triazolam (medicines used for anxiety or insomnia),
• warfarin or any other anticoagulant, e.g. dabigatran, rivaroxaban, apixaban, edoxaban (medicines used to thin the blood),
• carbamazepine, valproate, phenytoin (antiepileptic medicines),
• atorvastatin, rosuvastatin (statins – medicines lowering blood cholesterol levels),
• methylprednisolone (a very potent anti-inflammatory medicine),
• omeprazole (a medicine reducing gastric acid secretion),
• cilostazol (a medicine used to treat intermittent claudication – a disease characterised by pain in the lower limbs occurring during walking and resolving with rest),
• cyclosporine, tacrolimus, sirolimus (medicines used, among others, after organ transplantation),
• sildenafil, tadalafil, vardenafil (medicines used for erectile dysfunction),
• vinblastine (a medicine used in cancer chemotherapy),
• theophylline (a medicine used to treat bronchial asthma),
• tolterodine (a medicine used for urinary incontinence),
• phenobarbital (an anticonvulsant medicine),
• St. John’s wort (a herbal medicine used to treat mild depression),
• sulfonylureas, nateglinide, repaglinide, insulin (medicines used to treat diabetes),
• aminoglycosides (a group of antibiotics),

This is also important when using the following medicines:

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

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

Klarmin with food, drink and alcohol
Tablets may be taken with or without food.
Pregnancy, breastfeeding and fertility
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.
Klarmin may be used during pregnancy only if, in the doctor’s opinion, the benefit to the mother outweighs the potential risk to the foetus.
Since clarithromycin passes into human milk, breastfeeding women should exercise special caution when using Klarmin.
Driving and using machines
The medicine may cause dizziness, confusion and disorientation, which may affect the ability to drive or operate machinery.
Klarmin contains quinoline yellow
Quinoline yellow (a dye) may cause allergic reactions in sensitive individuals.
Klarmin contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to take Klarmin

This medicine should always be used as directed by the doctor. If in doubt, consult the doctor or pharmacist.
This is an oral medicine.
The tablet should be swallowed whole with water. Do not chew or suck the tablet.

Respiratory tract, skin and soft tissue infections, acute otitis media
Adults: in severe infections, one tablet (500 mg) twice daily (every 12 hours).
Treatment usually lasts from 5 to 14 days, except for pneumonia and sinusitis, when treatment lasts from 6 to 14 days.

Use in children and adolescents
Children above 12 years of age: dosage as in adults.
Children under 12 years of age: the use of clarithromycin in coated tablet form has not been studied in children under 12 years of age. In these children, clarithromycin oral suspension is recommended.

Patients with renal impairment: the doctor may recommend reducing the dose by half, meaning one tablet (250 mg) once daily. In severe infections – one tablet (250 mg) twice daily.
In such cases, use of Klarmin containing 250 mg clarithromycin per tablet is recommended. Treatment should not last longer than 14 days.

Infections caused by mycobacteria
Recommended dose in adults: one tablet 500 mg twice daily.
Treatment of disseminated infection caused by Mycobacterium avium complex (MAC) in AIDS patients should be continued as long as directed by the doctor. Klarmin should be used concomitantly with other anti-Mycobacterium agents.
Treatment of other non-tuberculous Mycobacterium infections should be continued according to the doctor’s instructions.

Prevention of MAC infections
Recommended dose in adults: one tablet (500 mg) twice daily.

Helicobacter pylori infections
In patients infected with Helicobacter pylori, one of the following treatment regimens is recommended.

Triple therapy:

• clarithromycin 500 mg twice daily (every 12 hours) with amoxicillin 1 g twice daily and lansoprazole 30 mg twice daily for 10 days; or
• clarithromycin 500 mg twice daily with amoxicillin 1 g twice daily and omeprazole 20 mg once daily for 7 to 10 days.

Dual therapy:

• clarithromycin 500 mg three times daily and omeprazole 40 mg daily for 14 days. Omeprazole 20 mg or 40 mg daily should be continued for the next 14 days; or
• clarithromycin 500 mg three times daily and lansoprazole 60 mg daily for 14 days. To achieve complete ulcer healing, further administration of acid-reducing medicines may be necessary.

Taking more Klarmin than recommended
If more Klarmin has been taken than recommended, contact a doctor or pharmacist immediately.
Taking a higher dose of Klarmin than recommended may cause gastrointestinal symptoms (vomiting, abdominal pain).

Missing a dose of Klarmin
If a dose of Klarmin is missed, take it as soon as possible, then take the next dose at the scheduled time.
Do not take a double dose to make up for a missed dose.

Stopping Klarmin treatment
Do not stop treatment, even if symptoms improve and disappear after a few days of treatment.
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.
You should contact your doctor immediately and go to the nearest hospital emergency department
if any of the following symptoms occur:
If the patient develops a severe skin reaction: red, peeling rash with lumps under the skin and blisters (erythema multiforme), contact your doctor immediately. The frequency of these adverse reactions is unknown (cannot be estimated from available data).
Adverse reactions reported with unknown frequency (frequency cannot be estimated from available data):

• sudden wheezing, difficulty breathing, swelling of eyelids, face or lips, rash or itching,
• severe rash with redness, fever, blisters or skin ulcers (Stevens-Johnson syndrome), severe rash with redness, peeling and itching of the skin resembling serious burns (toxic epidermal necrolysis [Lyell's syndrome]),
• rash, fever, abnormal blood test results and inflammation of internal organs. These may be symptoms of drug reaction with eosinophilia and systemic symptoms (DRESS),
• severe or prolonged diarrhoea, which may contain blood or mucus (pseudomembranous colitis). Diarrhoea may also occur after stopping clarithromycin treatment (see also "Warnings and precautions"),
• jaundice (yellowing of the skin or whites of the eyes), skin irritation, pale stools, dark urine, abdominal pain, loss of appetite. These symptoms may indicate liver dysfunction,
• dangerously rapid heartbeat, irregular heart rhythm, extra heartbeats,
• pancreatitis (severe pain in the upper abdomen radiating to the back with nausea and vomiting),
• kidney inflammation (presence of blood in urine, fever and back pain),
• muscle weakness, tenderness or pain, especially if the patient feels unwell or has a high temperature – this may be a sign of muscle breakdown which may lead to kidney problems (rhabdomyolysis).

Adverse reactions reported not very common (occur in 1 to 10 out of 1,000 patients):

• changes in ECG recording, palpitations (prolongation of QT interval),
• abnormal liver function test results.

Other adverse reactions:
In clinical studies and after marketing of clarithromycin, the following adverse reactions were reported commonly (occur in 1 to 10 out of 100 patients):

• insomnia,
• taste disturbances, headache, altered sense of taste,
• diarrhoea, vomiting, indigestion, nausea, abdominal pain,
• abnormal liver function tests,
• rash, excessive sweating.

Adverse reactions reported not very common (occur in 1 to 10 out of 1,000 patients):

• candidiasis (fungal infection), vaginal infection,
• decreased number of white blood cells, decreased number of neutrophils and increased number of eosinophils,
• hypersensitivity,
• anorexia, decreased appetite,
• restlessness,
• dizziness, drowsiness, tremor,
• balance disorders, hearing loss, tinnitus,
• gastritis, oral inflammation, glossitis, increased abdominal circumference, constipation, dry mouth, belching, flatulence,
• cholestasis (increased bile components in blood), hepatitis, increased liver enzyme activity,
• itching, urticaria,
• 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 marketing of clarithromycin in tablet and suspension forms, with unknown frequency (frequency cannot be estimated from available data):

• psychotic disorder, confusion, depersonalization, depression, disorientation, hallucinations, unusual dreams, mania,
• rosacea,
• agranulocytosis (reduction in neutrophil count),
• thrombocytopenia (reduction in platelet count),
• seizures, loss of taste, parosmia (distorted sense of smell), anosmia (loss of smell), paresthesia (numbness, tingling),
• deafness,
• bleeding and changes in blood clotting parameters (especially if the patient is simultaneously taking oral anticoagulants),
• tongue discoloration, tooth discoloration,
• liver failure, parenchymal jaundice,
• acne.

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

• nausea, vomiting, taste disturbances, constipation, abdominal pain, diarrhoea, flatulence, dry mouth,
• headache, hearing disturbances,
• rash,
• dyspnoea, insomnia,
• abnormal laboratory results: increased aspartate aminotransferase (AspAT) and alanine aminotransferase (AlAT) activity, increased blood urea nitrogen, and decreased platelet and white blood cell counts.

If any of the adverse reactions worsen or if any adverse reactions not listed in this leaflet occur, inform your doctor or pharmacist.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. 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
Phone: +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 Klarmin

Keep this medicine out of sight and reach of children.
Store below 25°C. Keep in the original packaging.
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. Such measures will help protect
the environment.

6. Contents of the pack and other information

What Klarmin contains
The active substance is clarithromycin: one coated tablet contains 500 mg of clarithromycin.
The other ingredients are: microcrystalline cellulose, sodium croscarmellose, colloidal silicon dioxide, povidone (E 1201), talc (E 553b), stearic acid (E 570), magnesium stearate (E 470b);
Coating ingredients: polyvinyl alcohol, titanium dioxide (E 171), quinoline yellow lake (E 104), soybean lecithin (E 322), xanthan gum (E 415).

What Klarmin looks like and contents of the pack
Klarmin 500 mg is an elongated, biconvex, film-coated tablet of light yellow colour.
The pack contains 14 or 28 film-coated tablets in blisters made of PVC/PE/PVDC/Aluminium, placed in a cardboard box with a patient information leaflet.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Bausch Health Ireland Limited
3013 Lake Drive
Citywest Business Campus
Dublin 24, D24PPT3
Ireland
Tel.: +48 17 865 51 00

Manufacturer
ICN Polfa Rzeszów S.A.
Przemysłowa 2 Street
35-959 Rzeszów
Poland