Klarmin

Patient Information Leaflet

Klarmin, 250 mg, film-coated tablets
Clarithromycinum
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, 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 pack and other information

1. What Klarmin is and what it is used for

Klarmin contains the active substance clarithromycin. It is a macrolide antibiotic that 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, cellulitis, abscesses,
• Dental and oral infections, e.g. periapical abscess, periodontitis,
• 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 to treat gout).
• 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 with concomitant renal insufficiency.
• If the patient is taking a medicine containing lomitapide.

Warnings and precautions
Before starting treatment with Klarmin, discuss this 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 consult a doctor who will initiate appropriate treatment;
• diarrhoea, especially severe or persistent – inform the doctor as soon as possible; if necessary, the doctor will recommend appropriate treatment; do not use antidiarrhoeal medicines;
• symptoms indicating liver dysfunction such as loss of appetite, jaundice, dark urine, itching or abdominal pain – discontinue treatment and immediately consult a 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:

• bacterial cross-resistance (bacteria resistant to clarithromycin may also show resistance to other macrolide antibiotics, as well as to lincomycin 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 that lower blood cholesterol levels),
• midazolam administered orally (a medicine used for anxiety or insomnia),
• colchicine (a medicine used to treat gout).

Inform your 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 that lower blood cholesterol levels),
• methylprednisolone (a very potent anti-inflammatory medicine),
• omeprazole (a medicine that reduces gastric acid secretion),
• cilostazol (a medicine used to treat intermittent claudication – a condition characterised by pain in the lower limbs during walking, which resolves 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 to treat 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, to treat rheumatoid arthritis, and for treatment or prevention of malaria). Taking these medicines together 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 body's immune response, which is useful in treating many different conditions).

Klarmin with food, drink and alcohol
Tablets may be taken with food or on an empty stomach.
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 use during pregnancy and breastfeeding has not been established.
Klarmin may be used during pregnancy 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, breastfeeding women should exercise particular caution when using Klarmin.
Driving and operating machinery
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.
If a single dose of 500 mg is required, it is recommended to use Klarmin tablets containing 500 mg of clarithromycin.

Respiratory tract, skin and soft tissue infections, acute otitis media
Adults: one tablet (250 mg) twice daily (every 12 hours).
In severe infections, the doctor may recommend increasing the dose to two 250 mg tablets (500 mg) twice daily (every 12 hours). Treatment usually lasts from 5 to 14 days, except for pneumonia and sinusitis, when treatment lasts 6 to 14 days.

Use in children and adolescents
Children over 12 years of age: dosage as in adults.
Children under 12 years of age: the use of clarithromycin in 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. Treatment should not last longer than 14 days.

Dental and oral infections
One tablet (250 mg) twice daily (every 12 hours). Treatment usually lasts 5 days.

Infections caused by mycobacteria
Recommended dose in adults: two 250 mg tablets (500 mg) twice daily.
Treatment of disseminated infection caused by Mycobacterium avium complex (MAC) in patients with AIDS should be continued as long as directed by the doctor. Klarmin should be used concurrently with other medicines active against Mycobacterium.
Treatment of other non-tuberculous Mycobacterium infections should be continued according to the doctor's instructions.

Prevention of MAC infections
Recommended dose in adults: two 250 mg tablets (500 mg) twice daily.

Helicobacter pylori infections
For 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 lanzoprazole 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 lanzoprazole 60 mg daily for 14 days. Further treatment with acid-reducing medicines may be necessary to completely heal the ulcer.

Taking more Klarmin than recommended
If more Klarmin has been taken than recommended, seek immediate advice from a doctor or pharmacist.
Taking a higher dose than recommended may cause gastrointestinal symptoms (vomiting, abdominal pain).

Missed 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 signs of illness disappear after a few days of taking the medicine.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets 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 severe 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 (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 function disorders,
• dangerously fast heartbeat, irregular heart rhythm, extra heartbeats,
• pancreatitis (severe pain in the upper abdomen radiating to the back with nausea and vomiting),
• kidney inflammation (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 can lead to kidney problems (rhabdomyolysis).

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

• changes in ECG, 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 have been reported commonly (occur in 1 to 10 out of 100 patients):

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

Adverse reactions reported not very commonly (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,
• anxiety,
• dizziness, drowsiness, tremor,
• balance disorders, hearing loss, tinnitus,
• gastritis, oral inflammation, glossitis, increased abdominal girth, constipation, dry mouth, belching, bloating with gas release,
• 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 tablets and suspension, with unknown frequency (frequency cannot be estimated from available data):

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

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

• nausea, vomiting, taste disturbances, constipation, abdominal pain, diarrhoea, bloating with gas release, dry mouth,
• headache, hearing disturbances,
• rash,
• shortness of breath, 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.

If any of the adverse effects worsen or if any adverse effects not listed in this leaflet occur, inform your doctor or pharmacist.
Reporting of adverse reactions
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring of 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 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 help protect the environment.

6. Contents of the pack and other information

What Klarmin contains
The active substance is clarithromycin: one coated tablet contains 250 mg of clarithromycin.
The other ingredients are: microcrystalline cellulose, pregelatinized starch, 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), soy lecithin (E 322), xanthan gum (E 415).

What Klarmin looks like and contents of the pack
Klarmin 250 mg is a yellow, elongated, biconvex coated tablet.
The pack contains 14 or 28 coated tablets in blisters made of PVC/PE/PVDC/Aluminium, placed in a cardboard box with an instruction 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
35-959 Rzeszów
Poland