Package leaflet: Information for the user

CLARITROL 500 mg film-coated tablets

Clarithromycin
Generic medicine
Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

What is in this leaflet

What CLARITROL is and what it is used for
What you need to know before taking CLARITROL
How to take CLARITROL
Possible side effects
How to store CLARITROL
Contents of the pack and other information

1. What CLARITROL is and what it is used for

Clarithromycin belongs to a group of antibiotics called macrolides. Clarithromycin works by destroying certain types of bacteria that cause specific infections.

Clarithromycin may be used to treat bacterial infections of the chest (bronchitis, bacterial pneumonia, and atypical pneumonia).
Infections of the upper respiratory tract (tonsillitis, pharyngitis).
Sinus infections.
Infections of the skin and underlying tissue layers (impetigo, erysipelas, folliculitis, furunculosis, and infected wounds).
Mycobacterial infections, localized or disseminated, caused by Mycobacterium avium or Mycobacterium intracellulare.
Localized infections due to Mycobacterium chelonae, fortuitum or kansasii.

Clarithromycin, in combination with reduced gastric acidity, is indicated for the eradication of Helicobacter pylori, thereby reducing the recurrence of peptic ulcer.

2. What you need to know before taking CLARITROL

Do not take CLARITROL if:

you are allergic to clarithromycin, to other macrolide antibiotics such as erythromycin or azithromycin, or to any of the other ingredients of this medicine (listed in section 6);
you are taking medicines called ergotamine or dihydroergotamine (for migraine);
you are taking medicines called terfenadine or astemizole (widely used for hay fever or allergies), or cisapride or domperidone (medicines used for stomach disorders), or pimozide (for mental health problems), as the combination with these drugs may sometimes cause serious disturbances in heart rhythm;
you are taking lovastatin or simvastatin (for high cholesterol);
you are taking ticagrelor, ivabradine, or ranolazine (for heart or circulatory problems);
you are taking colchicine (usually taken for gout);
you are taking midazolam (a medicine used as an anaesthetic);
you or someone in your family has a history of heart rhythm disorders (ventricular arrhythmia, including torsades de pointes) or an abnormal electrocardiogram (ECG, electrical recording of the heart) known as "QT interval prolongation";
you have abnormally low levels of potassium or magnesium in your blood (hypokalaemia or hypomagnesaemia);
you suffer from severe liver problems combined with kidney problems;
you are taking a medicine containing lomitapide.

If any of the above conditions apply to you, consult your doctor for advice on an alternative medicine.
CLARITROL is not recommended in children under 12 years of age.
Warnings and precautions
Talk to your doctor or pharmacist before taking CLARITROL if:

you are elderly (over 65 years old);
you have liver or kidney problems;
you have a fungal infection (e.g. thrush) or know you are at risk of this condition;
you have heart diseases, for example, severe heart failure or problems with heart blood vessels (coronary artery disease);
you have heart rhythm problems or a slow heart rate (bradycardia);
you are taking other medicines that may cause ear damage (ototoxic). In such cases, your doctor may prescribe tests to monitor vestibular and hearing function;
you are pregnant or breastfeeding.

Prolonged use of antibiotics, including clarithromycin, may lead to the emergence of resistant organisms.
In view of the increasing resistance of Streptococcus pneumoniae to macrolides, it is important that susceptibility testing be performed when prescribing clarithromycin for community-acquired pneumonia. In hospital-acquired pneumonia, clarithromycin should be used in combination with appropriate additional antibiotics.
Mild to moderate skin and soft tissue infections are most commonly caused by Staphylococcus aureus and Streptococcus pyogenes, both of which may be resistant to macrolides. Therefore, susceptibility testing is important. In cases where beta-lactam antibiotics cannot be used (e.g. due to allergy), other antibiotics such as clindamycin may be preferred first-line treatments.
If a severe acute hypersensitivity reaction occurs, such as anaphylaxis, Stevens-Johnson syndrome, or toxic epidermal necrolysis, clarithromycin therapy must be immediately discontinued and appropriate emergency treatment initiated.
Concomitant use of clarithromycin and lovastatin or simvastatin is contraindicated (see section “Contraindications”). Caution is required when prescribing clarithromycin with other statins.
Rhabdomyolysis has been reported in patients taking clarithromycin and statins. Patients should be monitored for signs and symptoms of myopathy.
When concomitant use of clarithromycin and statins cannot be avoided, it is recommended to prescribe the lowest available dose of the statin. Consideration should be given to using a statin (e.g. fluvastatin) whose metabolism is not dependent on CYP3A (see section “Interactions”).
Concomitant use of clarithromycin and oral hypoglycaemics (such as sulfonylureas) and/or insulin may cause significant hypoglycaemia. Close monitoring of blood glucose is recommended (see section “Interactions”).
When clarithromycin is co-administered with warfarin, there is a risk of severe bleeding, a significant increase in the International Normalized Ratio (INR), and a significant prolongation of prothrombin time (see section “Interactions”). INR and prothrombin time should be frequently monitored when patients are receiving clarithromycin together with oral anticoagulants.
Prolonged use of the drug, as with other antibiotics, may result in colonization by an increased number of non-susceptible bacteria and fungi. If superinfections develop, appropriate therapy should be promptly initiated.
Doctors should not prescribe clarithromycin to pregnant women without a thorough risk/benefit assessment, particularly during the first three months of pregnancy (see section “Pregnancy and Breastfeeding”).
Clarithromycin should be used with caution when administered concomitantly with medicines known to be inducers of the cytochrome CYP3A4 enzyme (see section “Interactions”).
With the use of almost all antibacterial agents, including clarithromycin, Clostridioides difficile-associated diarrhoea (CDAD) has been reported, ranging from mild diarrhoea to fatal colitis.
Caution is advised when administering clarithromycin concomitantly with other ototoxic medicines, especially aminoglycosides.
Monitoring of vestibular and auditory function should be performed during and after completion of therapy.
Currently, macrolides, including clarithromycin, are considered appropriate only for certain skin and soft tissue infections, such as those caused by Corynebacterium minutissimum, acne vulgaris, erysipelas, and in situations where penicillin therapy cannot be used.
Children
The use of CLARITROL is not recommended in children under 12 years of age.
Other medicines and CLARITROL
Inform your doctor or pharmacist if you have recently taken any other medicines, including those without a prescription. This is because CLARITROL may affect the action of other medicines, and some medicines may affect CLARITROL.
CLARITROL must not be taken with ergot alkaloids, astemizole, terfenadine, cisapride, domperidone, pimozide, ticagrelor, ranolazine, colchicine, certain medicines for high cholesterol, or medicines known to cause serious disturbances in heart rhythm (see section “Do not take CLARITROL if”).
Do not take CLARITROL if you are also taking midazolam, a medicine used as an anaesthetic.
It is particularly important that you inform your doctor if you are taking:

Ergotamine or dihydroergotamine (for migraine)
Astemizole (antihistamine), terfenadine (for hay fever or allergy), cisapride (for stomach disorders)
Ticagrelor or ranolazine (for heart attack, chest pain or angina)
Lovastatin, simvastatin or atorvastatin (treatments to lower blood cholesterol levels)
Colchicine (usually taken for gout)
Oral hypoglycaemics (repaglinide, nateglinide) and/or insulin
Other types of statins (other than lovastatin or simvastatin), medicines used to reduce blood cholesterol levels
Warfarin or any other anticoagulant, e.g. dabigatran, rivaroxaban, apixaban, edoxaban (used to thin the blood)
Rifampicin, phenytoin, carbamazepine, phenobarbital, rifapentine, St. John’s wort, rifabutin (CYP3A inducers)
Efavirenz, ritonavir, zidovudine, nevirapine, etravirine, atazanavir or saquinavir (antiviral medicines used to treat HIV)
Alprazolam (for anxiety)
Fluconazole (medicines for fungal infections)
Cilostazol (antiplatelet agent)
Sirolimus, Tacrolimus and Cyclosporine (immunosuppressants for organ transplant)
Disopyramide (antiarrhythmic)
Methylprednisolone (a corticosteroid)
Midazolam (sedative/hypnotic)
Pimozide (antipsychotic)
Ibrutinib or Vinblastine (for cancer treatment)
Sildenafil, tadalafil and vardenafil (to treat erectile dysfunction in adult men)
Tolterodine (medicine for urinary incontinence)
Medicines that cause an alteration in the electrocardiogram known as long QT syndrome or torsades de pointes
Omeprazole (for treatment of indigestion and gastric ulcers)
Verapamil, diltiazem or amlodipine (medicines for high blood pressure)
Aminoglycosides (a group of antibiotics)
Other medicines known to cause serious disturbances in heart rhythm.

Blood levels, and therefore the side effects, of the following medicines may increase if taken together with CLARITROL:

Quetiapine (an atypical antipsychotic medicine)
Digoxin, Quinidine (heart medicines)
Tacrolimus (for organ transplants)
Triazolam (sedative)
Theophylline (a medicine that helps breathing)
Valproate (a medicine for epilepsy)
Itraconazole (an antifungal medicine)
Oral anticoagulants

This is also important if you are taking medicines called:

Hydroxychloroquine or chloroquine (used to treat conditions including rheumatoid arthritis or for the treatment or prevention of malaria). Taking these medicines together with clarithromycin may increase the risk of abnormal heart rhythms and other heart-related side effects;
Corticosteroids, administered orally, by injection or by inhalation (used to help suppress the body’s immune system – this is useful in treating a wide range of conditions).

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
The safety of clarithromycin during pregnancy has not been established.
Therefore, its use during pregnancy is not recommended without a careful risk/benefit assessment.
Breastfeeding
The safety of clarithromycin during breastfeeding has not been established. Clarithromycin is excreted in breast milk.
Driving and using machines
There are no data on the effects of clarithromycin on the ability to drive or use machinery. The possibility of dizziness, vertigo, confusion, and disorientation occurring with the use of this medicine should be considered before patients drive or operate machinery.
CLARITROL contains less than 1 mmol (23 mg) of sodium per capsule, i.e. essentially 'sodium-free'.

3. How to take CLARITROL

Take this medicine exactly as directed by your doctor or pharmacist.
Severe infections: 500 mg every 12 hours. Treatment should continue, depending on the
severity of the infection, for up to 6–14 days.
Patients with renal impairment: the dose should be halved. In such patients, treatment should not
be continued for more than 14 days.
Mycobacterial infections: the starting dose is 500 mg twice daily. If no clinical or bacteriological
improvement is observed within 3–4 weeks, the daily dose may be increased to
1000 mg twice daily.
In the treatment of disseminated Mycobacterium Avium Complex infections in AIDS patients,
continue treatment until clinical or microbiological results are achieved, and always according to
the discretion of the treating physician.
Dosing regimen for eradication of Helicobacter pylori:
Triple therapy:
Clarithromycin 500 mg twice daily in combination with amoxicillin 1000 mg twice daily and omeprazole 20 mg daily for a period of 7 to 10 days.
Clarithromycin 500 mg twice daily in combination with lansoprazole 30 mg twice daily and amoxicillin 1000 mg twice daily for 10 days.
Dual therapy:
Clarithromycin 500 mg three times daily in combination with omeprazole 40 mg daily for 14 days, followed by omeprazole 20 mg or 40 mg daily for an additional 14 days.
Clarithromycin 500 mg three times daily in combination with lansoprazole 60 mg daily for 14 days. Further suppression of acid secretion may be required to reduce ulceration.
Clarithromycin has also been used in the following therapeutic regimens:

clarithromycin + tinidazole and omeprazole or lansoprazole
clarithromycin + metronidazole and omeprazole or lansoprazole
clarithromycin + tetracycline, bismuth subsalicylate, and ranitidine
clarithromycin + amoxicillin and lansoprazole
clarithromycin + ranitidine bismuth citrate

If you take more CLARITROL than you should
If you accidentally take more medicine than prescribed, you may experience stomach or
intestinal problems.
If you take high doses of CLARITROL, or if a child accidentally swallows some tablets, contact your doctor immediately or go to the nearest hospital emergency department.
If you forget to take CLARITROL
Take the missed dose as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take the next one at the regular time.
Do not take a double dose to make up for a forgotten dose.
If you stop taking CLARITROL
Do not stop taking this medicine before your doctor tells you to, even if you feel better, because symptoms may return.
If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, CLARITROL can cause side effects, although not everyone experiences them.
Following the instructions in this leaflet reduces the risk of side effects.
If any of the side effects worsen, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Stop taking CLARITROL immediately and contact your doctor if you experience any of the following:

Severe allergic reactions: swelling (angioedema) of the face, eyes, lips, tongue, and throat, breathing difficulties, increased heart rate with possible sudden drop in blood pressure (anaphylactic reactions);
Severe skin rashes with redness, blistering, and peeling, mouth, lip, and skin ulcers (Stevens-Johnson syndrome, toxic epidermal necrolysis);
Skin rash with fever and abnormalities in blood, lungs, heart, or liver (DRESS syndrome);
Weight loss, yellowing of the eyes or skin (jaundice), dark urine, pale stools, itching, or abdominal pain (possible signs of liver problems such as hepatitis, cholestasis, liver failure);
Severe or prolonged diarrhoea, presence of blood in diarrhoeic stools, even up to 2 months after the last dose (possible signs of pseudomembranous colitis caused by a bacterium called Clostridioides difficile). Contact your doctor immediately if you develop a severe skin reaction: red, scaly rash with pustule and blister formation (exanthematous pustulosis). The frequency of this reaction is unknown (cannot be estimated from the available data).

Contact your doctor if, during treatment with CLARITROL, you notice any of the following:
Common side effects (may affect up to 1 in 10 people)

Insomnia
Dysgeusia, headache, altered taste
Diarrhoea, vomiting, dyspepsia, nausea, abdominal pain
Abnormal liver function tests
Rash, hyperhidrosis

Uncommon side effects (may affect up to 1 in 100 people)

Candidiasis, infection, vaginal infection
Leucopenia, neutropenia, thrombocytosis, eosinophilia
Hypersensitivity
Anorexia, decreased appetite
Anxiety, dizziness, nervousness
Drowsiness, tremor
Vertigo, hearing disturbance, tinnitus
ECG showing QT interval prolongation, palpitations
Gastritis, stomatitis, glossitis, abdominal distension, constipation, dry mouth, eructation, flatulence
Cholestasis, hepatitis, increased alanine aminotransferase, increased aspartate aminotransferase, increased gamma-glutamyl transferase
Itching, urticaria, maculopapular rash
Muscle spasms
Malaise, pyrexia, asthenia, chest pain, chills, fatigue
Increased alkaline phosphatase in blood, increased lactate dehydrogenase in blood

Other side effects with frequency not known (frequency cannot be estimated from the available data):

Pseudomembranous colitis, erysipelas
Agranulocytosis, thrombocytopenia
Anaphylactic reaction, angioedema
Psychotic disorder, confusion, depersonalization, depression, disorientation, hallucinations, abnormal dreams, mania
Seizures, ageusia, parosmia, anosmia, paresthesia
Deafness
Torsade de pointes, ventricular tachycardia
Ventricular fibrillation
Haemorrhage
Acute pancreatitis
Tongue discoloration, tooth discoloration
Liver failure, hepatocellular jaundice
Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), acne
Red, scaly skin rash with pustule and blister formation (exanthematous pustulosis)
Rhabdomyolysis, myopathy
Abnormal urine colour, renal failure, interstitial nephritis
Increased international normalized ratio, prolonged prothrombin time

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store CLARITROL

Do not use this medicine after the expiry date stated on the label and the carton.
The expiry date refers to the last day of that month.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children.

6. Package contents and other information

Each film-coated tablet contains:
Active substance: clarithromycin 500 mg
Other components: sodium croscarmellose, pregelatinized starch, microcrystalline cellulose, anhydrous colloidal silica, povidone, stearic acid, magnesium stearate, talc, hypromellose, propylene glycol, sorbitan monoleate, vanillin, titanium dioxide (E-171), hydroxypropylcellulose, sorbic acid.
Description of the appearance of CLARITROL and package contents
Film-coated tablets for oral use. Blister pack containing 14 tablets.
Marketing Authorization Holder
S.F. GROUP S.r.l.
Via Tiburtina, n° 1143 - 00156 Rome
Manufacturer
SPECIAL PRODUCT’S LINE S.p.A.
Via Fratta Rotonda Vado Largo, n° 1 - 03012 Anagni (FR)