Package Insert: Information for the User

Claritromycin Unidía Kern Pharma 500 mg Modified Release Tablets

Read this package insert carefully before starting to take this medicine, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you and should not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

Claritromicina Unidía Kern Pharma is a macrolide antibiotic, active against germs that cause respiratory or skin infections.

Claritromicina is used to treat infections caused by sensitive germs inadults, adolescents aged 12 to 18 years, and children over 12 years:

• Upper respiratory tract infections, such as pharyngitis (throat infection causing sore throat), tonsillitis (infection of the tonsils) and sinusitis (infection of the paranasal sinuses around the forehead, cheeks, and eyes).
• Lower respiratory tract infections, such as acute bronchitis (infection and inflammation of the bronchi), exacerbation of chronic bronchitis (prolonged or recurring inflammation of the lungs) and bacterial pneumonias (inflammation of the lungs caused by bacteria).
• Mild skin and soft tissue infections, such as folliculitis (infection of one or more hair follicles), cellulitis (acute skin inflammation) and erysipelas (type of skin infection) (see warnings and precautions).

Do not take Claritromicina Unidía Kern Pharma

- If you are allergic to clarithromycin, other macrolide antibiotics such as erythromycin or azithromycin, or any of the other components of this medication (listed in section 6).

- If you have a creatinine clearance of less than 30 ml/min.

- If you have an irregular heart rhythm.

- If you have severe kidney and liver problems.

- If you are taking ergotamine or dihydroergotamine or using inhalers of ergotamine for migraine while taking clarithromycin. Consult your doctor for alternative medications.

- If you are taking medications called terfenadine, astemizol (allergy medication), cisaprida or domperidona (used for stomach problems) or pimozida (used to treat certain psychiatric disorders) as taking these medications with clarithromycin may cause severe heart rhythm disturbances.

Consult your doctor for alternative medications.

- If you are taking ticagrelor (to prevent blood clots in your veins and used in heart attacks and other heart problems), ivabradina or ranolazina (for angina or to reduce the risk of heart attack or stroke).

- If you are taking other medications known to cause severe heart rhythm disturbances.

- If you are being treated with midazolam oral (for anxiety or to help you fall asleep).

- If you have abnormally low levels of potassium or magnesium in your blood (hypokalemia or hypomagnesemia).

- If you or a family member has a history of heart rhythm disorders (ventricular arrhythmia, including Torsade de Pointes) or abnormal electrocardiogram (ECG, heart electrical recording) called "prolongation of QT syndrome).

- If you are taking medications called lovastatina or simvastatina (to lower cholesterol levels), as the combination of these medications may increase the risk of adverse effects. Consult your doctor for alternative medications.

- If you are taking colchicine (for gout).

- If you are taking lomitapida.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Claritromicina Unidía Kern Pharma

- If you have heart, kidney, or liver problems.

- If you have or are prone to fungal infections (e.g., mouth ulcers).

- If you are pregnant or breastfeeding.

- If you are taking medications known as colchicine, triazolam, midazolam (for anxiety or insomnia), lovastatina, simvastatina.

- If you are diabetic and taking hypoglycemic medications (medications to lower blood sugar levels such as nateglinida, pioglitazona, rosiglitazona, and repaglinida, sulfonilureas, or insulin) and clarithromycin may lower blood sugar levels too much. Careful monitoring of blood sugar levels is recommended.

- If you are taking a medication called warfarina or another anticoagulant, such as dabigatrán, rivaroxabán, apixabán, edoxabán (used to thin the blood).

- If you have myasthenia gravis, a condition where your muscles weaken and tire easily.

- If you develop severe or prolonged diarrhea during or after taking clarithromycin, consult your doctor immediately.

If any of these situations affect you, consult your doctor before taking clarithromycin.

Children and adolescents

Do not administer this medication to children under 12 years old.

Older patients

Since clarithromycin is eliminated by the liver and kidneys, caution should be exercised in patients with liver insufficiency, moderate or severe renal insufficiency, and in elderly patients.

Other medications and Claritromicina Unidía Kern Pharma

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including those purchased without a prescription.

Do not take Claritromicina Unidía Kern Pharma with ergot alkaloids, astemizol, terfenadine, cisaprida, domperidona, pimozida, ticagrelor, ranolazina, colchicine, certain medications for high cholesterol, or medications known to cause severe heart rhythm disturbances.

This is especially important if you are taking medications for:

- Heart problems (e.g., digoxina, verapamilo, quinidina, or disopiramida).

- Blood thinners (e.g., warfarina or another anticoagulant, such as dabigatrán, rivaroxabán, apixabán, edoxabán).

- Migraine (e.g., ergotamine or dihydroergotamine).

- Epilepsy or bipolar disorder (carbamazepina, valproato, fenobarbital, or phenytoin).

- High cholesterol (e.g., simvastatina or lovastatina).

Or if you are taking any medication called:

- Theophylline (used in patients with breathing difficulties, such as asthma).

- Triazolam, alprazolam, or midazolam (sedatives).

- Cilostazol (for poor circulation).

- Methylprednisolone (a corticosteroid).

- Ibrutinib or vinblastine (for cancer treatment).

- Cyclosporine (immunosuppressant).

- Rifabutina (for the treatment of certain infections).

- Tacrolimus or sirolimus (for organ transplants and severe eczema).

- Sildenafil, tadalafil, or vardenafil (to treat erectile dysfunction in adult men or for pulmonary hypertension).

- Zidovudine (for viruses).

- St. John's Wort (herbal product for depression).

- Phenobarbital (medication for epilepsy).

- Nevirapina and efavirenz may decrease clarithromycin levels.

- Rifampicin or rifapentina (for tuberculosis).

- Omeprazol (for stomach acid and ulcers).

- Ritonavir (antiviral medication used in HIV treatment) may increase clarithromycin levels. The combination of atazanavir, etravirina, and saquinavir (also antiviral medications used in HIV treatment) with clarithromycin may increase both atazanavir (or saquinavir) and clarithromycin levels.

- Itraconazol (antifungal medication) taken with clarithromycin may increase both medication levels.

- Fluconazol, another antifungal medication, may increase clarithromycin levels.

- Tolterodina (for overactive bladder syndrome). In some patients, tolterodina levels may increase when taken with clarithromycin.

- Quetiapina (for schizophrenia or other psychiatric conditions).

- Beta-lactam antibiotics (certain penicillins and cephalosporins).

- Aminoglycosides (used as antibiotics for infections).

- Calcium channel blockers (medications for high blood pressure).

- Hydroxychloroquine or chloroquine (used to treat conditions such as rheumatoid arthritis, or to treat or prevent malaria). Taking these medications with clarithromycin may increase the risk of abnormal heart rhythms and other severe adverse reactions affecting the heart.

- Corticosteroids, administered orally, by injection, or inhaled (used to suppress the immune system; this is useful in the treatment of a wide variety of diseases).

Taking Claritromicina Unidía Kern Pharma with food and drinks

Claritromicina Unidía Kern Pharma tablets should be taken always with food.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

The safety of clarithromycin during pregnancy has not been established, so your doctor will weigh the benefits against the potential risk, especially during the first three months of pregnancy.

Claritromycin passes into breast milk, so it is recommended to stop breastfeeding during treatment with clarithromycin.

Driving and operating machinery

Since clarithromycin may cause dizziness, vertigo, confusion, and disorientation, during treatment with clarithromycin, you should exercise extreme caution when driving or operating hazardous machinery.

Claritromicina Unidía Kern Pharma contains lactose

This medication contains lactose. If your doctor has told you that you have a certain sugar intolerance, consult with them before taking this medication.

Clarithromycin is administered orally.

Follow exactly the administration instructions for clarithromycin indicated by your doctor. Consult your doctor or pharmacist if you have any doubts.

Adults, adolescents 12 to 18 years old, and children over 12 years old:The usual recommended dose of clarithromycin for adults is 1 tablet of 500 mg, once a day. The usual duration of treatment is 5 to 14 days, excluding community-acquired pneumonia and sinusitis treatment that requires 6 to 14 days of therapy.

In severe cases, your doctor may instruct you to take 2 tablets (1g), once a day.

Do not crush or chew the clarithromycin tablets.

Take the clarithromycin tablets always with food and a glass of water. Remember to take your medicine. Take the tablets at the same time every day.

Your doctor will indicate the duration of your treatment with clarithromycin.

Renal insufficiency

In patients with renal insufficiency and a creatinine clearance less than 30 ml/min, the clarithromycin dose should be reduced to half, i.e., 250 mg once a day, or 250 mg twice a day in more severe infections. In these patients, treatment should be interrupted after 14 days. Since the tablet cannot be divided, the daily dose cannot be less than 500 mg/day, so clarithromycin should not be administered in this group of patients. For patients with moderate renal function (creatinine clearance of 30 to 60 ml/min), a 50% dose reduction should be implemented, resulting in a maximum dose of one modified-release clarithromycin tablet per day.

If you take more Clarithromycin Unidía Kern Pharma than you should

If you have taken more clarithromycin than you should, you can expect the appearance of digestive disorders. Consult your doctor or pharmacist immediately, as they will try to quickly eliminate the clarithromycin that your body has not yet absorbed. Hemodialysis or peritoneal dialysis are not effective.

In case of overdose or accidental ingestion, consult the Toxicological Information Service, phone 91.562.04.20, indicating the medication and the amount ingested.

If you forgot to take Clarithromycin Unidía Kern Pharma

Do not take a double dose to compensate for the missed doses. Take the tablet as soon as possible and continue taking it every day at the same time.

If you interrupt treatment with Clarithromycin Unidía Kern Pharma

Do not discontinue treatment prematurely, as your disease may worsen or recur. If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medicines, Claritromicina Unidía Kern Pharma may cause side effects, although not everyone will experience them.

Side effects are classified as very common (may affect more than 1 in 10 patients), common (may affect up to 1 in 10 patients), uncommon (may affect up to 1 in 100 patients), and unknown frequency (cannot be estimated from available data).

The most common and more common adverse reactions related to treatment with clarithromycin, both in adults and children, are abdominal pain, diarrhea, nausea, vomiting, and taste alteration. These adverse reactions are usually mild in intensity and coincide with the known safety profile of macrolide antibiotics (see below).

No significant differences were observed in the incidence of these gastrointestinal adverse reactions during clinical trials between patients with or without pre-existing mycobacterial infections.

Summary of side effects

Side effects are described in order of decreasing severity within the same body system:

• Very common (may affect more than 1 in 10 patients, with the intravenous formulation): phlebitis (inflammation of the vein) at the injection site.
• With all clarithromycin-containing medicines, the following have been observed with common frequency (may affect up to 1 in 10 patients):

- Digestive system: diarrhea, vomiting, dyspepsia (digestive disorder that makes digestion difficult), nausea, abdominal pain.

- Nervous system: taste alteration, headache, taste alteration.

- Skin: mild skin eruptions, excessive sweating.

- Psychiatric disorders: insomnia.

- Vascular disorders: vasodilation.

- Liver disorders: abnormal liver function tests.

- Administration site disorders: pain and inflammation at the injection site (only with the intravenous formulation).

• Less common (may affect up to 1 in 100 patients) have been observed the following:

- Infections: cellulitis (only with the intravenous formulation), candidiasis (infection by a type of fungus), gastroenteritis (only with prolonged-release tablets), infection (only with oral suspension granules), vaginal infection.

- Blood abnormalities: decreased white blood cells, decreased neutrophils (a type of white blood cell, only with immediate-release tablets), increased platelets, and, to a lesser extent, increased red and white blood cells in the blood (only with oral suspension granules), increased eosinophils (a type of white blood cell, only with immediate-release tablets).

- Immune system: anaphylactoid reaction (generalized allergic reaction, only with intravenous formulation), hypersensitivity (exaggerated allergic reaction to external agents).

- Nutritional disorders: anorexia, decreased appetite.

- Psychiatric disorders: anxiety and nervousness (the latter only with oral suspension granules).

- Nervous system: loss of consciousness and difficulty moving (both effects, only with intravenous formulation), dizziness, somnolence, tremors.

- Ear and balance: vertigo, hearing problems, tinnitus.

- Heart disorders: cardiac arrest and alteration of heart rhythm (fibrillation of the auricle) (both effects, only with intravenous formulation), prolongation of the QT interval (electrocardiogram indicator of potential ventricular arrhythmias), extrasystoles (premature heartbeat, only with intravenous formulation), palpitations (alterations in heartbeats).

- Respiratory disorders: asthma (difficulty breathing, chest tightness, and nocturnal or morning cough, only with intravenous formulation), nasal hemorrhages (only with prolonged-release tablets), pulmonary embolism (blockage of the pulmonary artery that causes chest pain on one side, cough, and difficulty breathing, only with intravenous formulation).

- Gastrointestinal disorders: esophagitis (inflammation of the esophagus, only with intravenous formulation), gastroesophageal reflux disease (damage to the esophagus that causes burning sensation, chronic cough, lack of air, and difficulty swallowing, only with prolonged-release tablets), gastritis (inflammation of the stomach lining), anal and rectal pain (only with prolonged-release tablets), oral mucosa inflammation, tongue inflammation, abdominal distension (only with immediate-release tablets), constipation, dry mouth, belching, flatulence.

- Liver disorders: decreased or suppressed bile flow into the intestine and liver inflammation (hepatitis) (both effects, only with immediate-release tablets), increased alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase (liver enzymes, only with immediate-release tablets).

- Skin: dermatitis bullous (vesicular eruptions, only with intravenous formulation), pruritus, urticaria (edematous, red, and itchy skin lesions), maculopapular eruption (skin lesion with a papule or wart on a patch, only with oral suspension granules).

- Musculoskeletal disorders: muscle spasms (only with oral suspension granules), musculoskeletal rigidity (only with intravenous formulation), muscle pain (only with prolonged-release tablets).

- Kidney disorders: increased serum creatinine and urea (both effects, indicating impaired kidney function, only with intravenous formulation).

- General disorders: malaise (only with immediate-release tablets), chest pain, chills, and fatigue (the latter three, only with immediate-release tablets).

- Laboratory tests: abnormal albumin-globulin ratio (only with intravenous formulation), increased serum alkaline phosphatase, and increased lactate dehydrogenase in the blood (both effects, only with immediate-release tablets).

• Unknown frequency (cannot be estimated from available data) have been observed the following:

- Infections: pseudomembranous colitis (diarrhea that can be severe), erysipelas (skin redness of variable extent that can cause pain, itching, and fever).

- Blood abnormalities: decreased neutrophils (a type of white blood cell), decreased platelets.

- Immune system: anaphylactic reaction (generalized allergic reaction), angioedema (subcutaneous swelling).

- Metabolism: decreased blood glucose concentration.

- Psychiatric disorders: psychotic disorder, confusion, depersonalization, depression, disorientation, hallucinations, and daydreaming (perceptions of external stimuli attenuated).

- Nervous system: convulsions, decreased or lost sense of taste, altered sense of smell, lost or decreased sense of smell, paresthesia, numbness, or tingling in hands, feet, arms, or legs.

- Ear: deafness.

- Heart disorders: torsades de pointes (a type of ventricular tachycardia), ventricular tachycardia (acceleration of heartbeats with more than 100 beats per minute with at least 3 irregular consecutive beats).

- Vascular disorders: hemorrhage.

- Gastrointestinal disorders: acute pancreatitis (inflammation of the pancreas), tongue discoloration, tooth discoloration.

- Liver disorders: liver function failure, icteric hepatocellular (yellow discoloration of the skin and eyes).

- Skin: Stevens-Johnson syndrome (generalized eruption with blisters and skin peeling, primarily affecting genital, oral, and trunk areas), generalized acute exanthematous pustulosis (generalized scaly eruption with red color, with subcutaneous nodules and blisters, accompanied by fever, primarily located in skin folds, trunk, and upper limbs), and toxic epidermal necrolysis (generalized eruption with blisters and skin peeling, particularly around the mouth, nose, eyes, and genital areas, causing generalized skin peeling (more than 30% of body surface area), systemic symptoms such as fever, glandular inflammation, and abnormal blood test results (such as eosinophilia and elevated liver enzymes)).

- Musculoskeletal disorders: rhabdomyolysis (muscle breakdown that can cause kidney damage), myopathy (muscle disease of multiple causes).

- Kidney disorders: kidney function failure, interstitial nephritis (inflammation of the renal tubules).

- Laboratory tests: increased international normalized ratio (calculation to detect blood coagulation), prolonged prothrombin time (indicates a coagulation disorder), and abnormal urine color.

Specific side effects

Flebitis at the injection site, pain at the injection site, pain at the venipuncture site, and inflammation at the injection site are specific to the intravenous formulation of clarithromycin.

After marketing, reports of central nervous system effects (e.g., somnolence and confusion) with the simultaneous use of clarithromycin and triazolam have been received. Monitoring of the patient is suggested.

In some of the reports of rhabdomyolysis (muscle disease that can cause kidney damage), clarithromycin was administered concomitantly with statins, fibrates, colchicine, or allopurinol.

Rarely, reports of prolonged-release tablets of clarithromycin appearing in the feces have been received, many of these cases have occurred in patients with anatomical or functional gastrointestinal disorders (including ileostomy or colostomy) or with a shortened gastrointestinal transit time. In several reports, the presence of tablets in the feces has occurred in the context of diarrhea. It is recommended that patients who present tablets in the feces and do not experience improvement switch to another formulation of clarithromycin (e.g., suspension) or another antibiotic.

Side effects in children and adolescents:

The frequency, type, and severity of adverse reactions in children are expected to be the same as in adults.

Immunocompromised patients

In patients with AIDS and other patients with damaged immune systems, treated with high doses of clarithromycin for long periods of time for mycobacterial infections, it is often difficult to distinguish side effects possibly associated with clarithromycin administration from those caused by the disease or other diseases that the patient may have in addition to AIDS.

In adult patients treated with daily total doses of 1,000 mg and 2,000 mg of clarithromycin, the most common adverse reactions that appeared were: nausea, vomiting, taste alteration, abdominal pain, diarrhea, skin rash, flatulence, headache, constipation, hearing abnormalities, and elevated transaminases (which may indicate liver, pancreas, heart, or muscle damage). Less frequently, difficulty breathing, insomnia, and dry mouth appeared. Incidences were similar in patients treated with 1,000 mg and 2,000 mg, but generally were 3 to 4 times more frequent in those who received a daily total dose of 4,000 mg of clarithromycin.

In these immunocompromised patients, around 2% to 3% who received daily 1,000 mg or 2,000 mg of clarithromycin presented severely abnormal elevated transaminases, as well as abnormally low white blood cell and platelet counts. A smaller percentage of patients in both dosing groups had elevated serum urea nitrogen levels (which may indicate impaired kidney function). In patients who received daily 4,000 mg, slightly higher incidences of abnormal values in all parameters, except white blood cell count, were observed.

Consult a doctor as soon as possible if you experience a severe skin reaction: a red, scaly rash with subcutaneous nodules and blisters (pustular exanthema). The frequency of this side effect is considered unknown (cannot be estimated from available data).

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicinal Products for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep out of the sight and reach of children.

No special storage conditions are required.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and the

medicines you no longer need at the Sigre Pointof the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and the medicines you no longer need. By doing so, you will help protect the environment.

Composition of Claritromicina Unidía Kern Pharma

• The active ingredient is clarithromycin. Each tablet contains 500 mg of clarithromycin (as clarithromycin citrate)
• The other components are: magnesium stearate, hypromellose, phthalate hypromellose, lactose monohydrate, talc, and opadry II yellow (hypromellose, lactose monohydrate, polyethylene glycol, quinoline yellow, aluminum lake, titanium dioxide).

Appearance of the product and content of the packaging

Modified-release tablets, oval, biconvex, yellow in color. Each package contains 14 or 20 tablets (standard package) and 500 tablets (clinical package).

Holder of the marketing authorization and responsible for manufacturing

Kern Pharma, S.L.

Venus, 72 – Pol. Ind. Colón II

08228 Terrassa -Barcelona

Spain

Last review date of this leaflet:February 2024

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www. aemps.es/