CLARITHROMYCIN KERN PHARMA 500 mg FILM-COATED TABLETS

1. What is Clarithromycin Kern Pharma and what is it used for

Clarithromycin is a medicine that belongs to the group of macrolide antibiotics and acts by eliminating bacteria.

Antibiotics are used to treat bacterial infections and are not effective against viral infections such as the flu or the common cold.

It is essential that you follow the instructions regarding the dose, intake, and duration of treatment indicated by your doctor.

Do not store or reuse this medicine. If you have any leftover antibiotic after finishing the treatment, return it to the pharmacy for proper disposal. Do not throw away medicines via wastewater or household waste.

Clarithromycin is used to treat infections caused by sensitive germs in:

Adults and adolescents from 12 to 18 years:

• Infections of the upper respiratory tract, such as pharyngitis (infection of the pharynx that causes sore throat), tonsillitis (infection of the tonsils), and sinusitis (infection of the paranasal sinuses that are around the forehead, cheeks, and eyes).
• Infections of the lower respiratory tract, such as acute bronchitis (infection and inflammation of the bronchi), exacerbation of chronic bronchitis (worsening of prolonged and repetitive lung inflammation), and bacterial pneumonia (inflammation of the lungs caused by bacteria). (See section warnings and precautions)
• Infections of the skin and soft tissues, such as folliculitis (infection of one or more hair follicles), cellulitis (acute inflammation of the skin), and erysipelas (a type of skin infection). (See section 2 warnings and precautions)
• Gastric or duodenal ulcer
• Prevention and treatment of infections caused by mycobacteria (a type of bacteria).

2. What you need to know before you take Clarithromycin Kern Pharma

Do not take Clarithromycin Kern Pharma

• If you are allergic to clarithromycin, to other macrolide antibiotics such as erythromycin or azithromycin, or to any of the other components of this medicine (listed in section 6)
• If you have a creatinine clearance of less than 30 ml/min.
• If you have an irregular heartbeat.
• If you have severe kidney and liver problems.
• If you are taking ergotamine or dihydroergotamine or use ergotamine inhalers for migraine while taking clarithromycin. Consult your doctor for alternative medications.
• If you are taking medications called terfenadine, astemizole (medication for hay fever or allergies), cisapride, or domperidone (used for stomach problems) or pimozide (medication used to treat certain psychiatric disorders), as taking these medications with clarithromycin can cause severe heart rhythm disturbances. Consult your doctor for alternative medications.
• If you are taking ticagrelor (to prevent the formation of blood clots in your veins and used in heart attacks and other heart problems), ivabradine, or ranolazine (for angina pectoris or to reduce the risk of heart attack or stroke).
• If you are taking other medications that are known to cause severe heart rhythm disturbances.
• If you are undergoing treatment with midazolam oral (for anxiety or to help fall asleep)
• If you or a family member have a history of heart rhythm disorders (ventricular cardiac arrhythmia, including Torsade de Pointes) or abnormalities in the electrocardiogram (ECG, electrical record of the heart) called "QT prolongation syndrome".
• If you are taking medications called lovastatin or simvastatin (to lower cholesterol levels), as the combination of these medications can increase the appearance of side effects. Consult your doctor for alternative medications.
• If you are taking colchicine (for gout)
• If you are taking a medication with lomitapide.
• If you have abnormally low levels of potassium or magnesium in the blood (hypokalemia or hypomagnesemia).

Warnings and precautions

Consult your doctor or pharmacist before starting to take clarithromycin

• If you have heart, kidney, or liver problems.
• If you have or are prone to fungal infections (e.g., thrush).
• If you are pregnant or breastfeeding
• If you are taking medications known as colchicine, triazolam, midazolam (for anxiety or insomnia), lovastatin, simvastatin.
• If you are diabetic and taking hypoglycemic agents (medications to lower blood sugar levels, such as nateglinide, pioglitazone, rosiglitazone, and repaglinide, sulfonylureas, or insulin), as clarithromycin may lower blood sugar levels too much. Careful monitoring of glucose levels is recommended.
• If you are taking a medication called warfarin or another anticoagulant, such as dabigatran, rivaroxaban, apixaban, edoxaban (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 medicine to children under 12 years of age; other presentations are available for this age group (granules for oral suspension).

Elderly patients

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

Taking Clarithromycin Kern Pharma with other medicines

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription.

Do not take clarithromycin with ergot alkaloids, astemizole, terfenadine, cisapride, domperidone, pimozide, ticagrelor, ranolazine, colchicine, some medications for high cholesterol, and medications known to cause severe heart rhythm disturbances (see Do not take Clarithromycin Kern Pharma).

This is especially important if you are taking medications for:

• Heart problems (e.g., digoxin, verapamil, quinidine, or disopyramide).
• Thinning the blood (e.g., warfarin or any other anticoagulant like dabigatran, rivaroxaban, apixaban, edoxaban).
• Migraine (e.g., ergotamine or dihydroergotamine).
• Epilepsy or bipolar disorder (carbamazepine, valproate, phenobarbital, or phenytoin).
• High cholesterol (e.g., simvastatin or lovastatin).

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).
• Rifabutin (for the treatment of certain infections).
• Tacrolimus or sirolimus (for organ transplants and severe eczema).
• Sildenafil, tadalafil, or vardenafil (for treating impotence in adult men or for pulmonary arterial hypertension).
• Zidovudine (for treating viruses).
• St. John's Wort (a herbal product for treating depression).
• Phenobarbital (a medication for treating epilepsy).
• Nevirapine and efavirenz may decrease clarithromycin levels.
• Rifampicin or rifapentine (for treating tuberculosis).
• Omeprazole (for treating stomach acid and stomach or intestinal ulcers).
• Ritonavir (an antiviral medication used in the treatment of HIV infection) may increase clarithromycin levels. The concomitant use of atazanavir, etravirine, and saquinavir (also antiviral medications used in the treatment of HIV infection) with clarithromycin may increase both atazanavir (or saquinavir) and clarithromycin levels.
• Itraconazole (an antifungal) taken with clarithromycin may increase the levels of both medications.
• Fluconazole, another antifungal medication, may increase clarithromycin levels.
• Tolterodine (for treating symptoms of overactive bladder). In some patients, tolterodine levels may increase when taken with clarithromycin.
• Quetiapine (for schizophrenia or other psychiatric conditions).
• Beta-lactam antibiotics (certain penicillins and cephalosporins)
• Aminoglycosides (used as antibiotics to treat infections).
• Calcium channel blockers (medications for treating high blood pressure).
• Hydroxychloroquine or chloroquine (used to treat diseases such as rheumatoid arthritis or to treat or prevent malaria). Taking these medications at the same time as clarithromycin may increase the risk of abnormal heart rhythms and other severe adverse reactions that affect the heart.
• Corticosteroids, administered orally, by injection, or inhaled (used to suppress the immune system; this is useful in the treatment of a wide range of diseases).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

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

Breastfeeding

Clarithromycin is excreted in breast milk, so breastfeeding should be interrupted during treatment with clarithromycin.

Driving and using machines

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

Warnings about excipients

This medicine contains less than 23 mg of sodium (1 mmol) per tablet; it is essentially "sodium-free".

3. How to take Clarithromycin Kern Pharma

Follow these instructions unless your doctor has given you different instructions. If in doubt, consult your doctor or pharmacist again.

Clarithromycin is presented in film-coated tablets for oral administration. Take the tablets at the same time every day.

The recommended doses are:

Adults and children over 12 years:

Patients with respiratory tract, skin, and soft tissue infections

The recommended dose is 250 mg twice a day for 7 days, although in more severe infections, the dose may be increased to 500 mg twice a day. The usual duration of treatment is 5 to 14 days, excluding community-acquired pneumonia and sinusitis, which require 6 to 14 days of therapy.

This pharmaceutical form is not suitable for administering doses less than 250 mg or for patients who have swallowing problems.

Eradiation of Helicobacter pylori in patients with duodenal ulcers (adults):

In patients with peptic ulcer associated with Helicobacter pylori, the recommended treatments are: Triple therapy: one tablet of clarithromycin 500 mg twice a day, with 30 mg of lansoprazole, twice a day, and 1000 mg of amoxicillin twice a day for 10 days. Or one tablet of clarithromycin 500 mg with 1000 mg of amoxicillin and 20 mg of omeprazole, all administered twice a day, for 7 to 10 days.

Patients with mycobacterial infections:

The recommended average dose for the prevention and treatment of mycobacterial infections is one tablet of clarithromycin 500 mg every 12 hours. The duration of treatment should be established by the doctor.

Patients with renal insufficiency:

In patients with renal insufficiency and a creatinine clearance of less than 30 ml/min, the dose of clarithromycin 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 at 14 days.

Follow these instructions unless your doctor has given you different instructions.

Since Clarithromycin Kern Pharma 500 mg cannot be divided, use the 250 mg presentation.

Remember to take your medicine. Take the tablets at the same time every day.

Your doctor will indicate the duration of your treatment.

If you think the effect of clarithromycin is too strong or too weak, tell your doctor or pharmacist.

Elderly patients

As for adults.

Use in children and adolescents

There are suitable presentations of clarithromycin for children from 6 months and adolescents under 12 years (granules for oral suspension)

If you take more Clarithromycin Kern Pharma than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount ingested. It is recommended to bring the leaflet and the package to the healthcare professional. The most frequent symptoms accompanying an overdose are gastrointestinal disorders. Neither hemodialysis nor peritoneal dialysis is effective.

If you have taken more clarithromycin than you should, you can expect the appearance of gastrointestinal disorders, and consult your doctor or pharmacist immediately, as they will try to eliminate the clarithromycin that your body has not yet absorbed.

If you forget to take Clarithromycin Kern Pharma

Do not take a double dose to make up for forgotten doses.

Take the tablet as soon as you remember and continue respecting the 12-hour interval between doses.

If you stop taking Clarithromycin Kern Pharma

Your doctor will indicate the duration of your treatment with clarithromycin. Do not stop treatment before, as your illness could worsen or reappear, even if you feel better.

If you have any other questions about the use of this product, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, clarithromycin can cause adverse effects, although not all people suffer from them.

The frequencies have been defined as follows:

Very frequent: may affect more than 1 in 10 patients

Frequent: may affect up to 1 in 10 patients

Infrequent: may affect up to 1 in 100 patients

Unknown frequency: cannot be estimated from the available data

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

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

Summaryof Adverse Effects

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

? It has been very frequently observed (may affect more than 1 in 10 patients, with the intravenous injection formulation): phlebitis (inflammation of the vein) at the injection site.

? With all medicines containing clarithromycin, the following have been frequently observed (may affect up to 1 in 10 patients):

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

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

- Skin: mild skin rashes, excessive sweating.

- Psychiatric disorders: insomnia.

- Vascular disorders: dilation of blood vessels in the body (vasodilation).

- Liver disorders: abnormal liver function tests.

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

? Infrequent (may affect up to 1 in 100 patients) the following have been observed:

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

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

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

- Eating 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 the intravenous injection formulation), dizziness, somnolence, tremors.

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

- Heart disorders: cardiac arrest and alteration of heart rhythm (atrial fibrillation) (both effects, only with the intravenous injection formulation), prolongation of the QT interval (indicator of the electrocardiogram that arrhythmias may occur), extrasystoles (anticipation of a heartbeat with respect to the normal heart rate, only with the intravenous injection formulation), palpitations (alterations in heartbeats).

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

- Gastrointestinal disorders: esophagus inflammation (only with the intravenous injection formulation), gastroesophageal reflux disease (damage to the esophagus that causes a burning sensation, chronic cough, shortness of breath, and difficulty swallowing, only with prolonged-release tablets), stomach mucosa inflammation (gastritis), pain in the anus and rectum (only with prolonged-release tablets), oral mucosa inflammation, tongue inflammation, abdominal distension (only with immediate-release tablets), constipation, dry mouth, belching, flatulence.

- Liver disorders: decrease or suppression of bile flow to the intestine and liver inflammation (hepatitis) (both effects, only with immediate-release tablets), increase in alanine aminotransferase (liver enzyme), aspartate aminotransferase (another liver enzyme), and gamma-glutamyltransferase (another liver enzyme, only with immediate-release tablets).

- Skin: bullous dermatitis (bullous rashes, only with the intravenous injection formulation), itching, urticaria (edematous, red, and very itchy skin lesions), maculopapular rash (skin lesion with a papule or wart on a stain, only with oral suspension granules).

- Muscle disorders: muscle spasms (only with oral suspension granules), musculoskeletal stiffness (only with the intravenous injection formulation), muscle pain (only with prolonged-release tablets).

- Kidney disorders: increase in serum creatinine and urea, (both effects, which indicate poorer kidney function, only with the intravenous injection formulation).

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

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

? With unknown frequency (its frequency cannot be determined with the available data) the following have been observed:

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

- Blood disorders: decrease in neutrophils (a type of white blood cell), decrease in platelets.

- Immune system: anaphylactic reaction (generalized allergic reaction), angioedema (swelling under the skin).

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

- Nervous system: convulsions, decrease or loss of taste, alteration of smell, loss or decrease of smell, sensation of tingling, numbness, or prickling 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/minute with at least 3 consecutive irregular beats).

- Vascular disorders: hemorrhage.

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

- Liver disorders: liver failure, hepatocellular jaundice (yellowing of the skin and eyes).

- Skin: Stevens-Johnson syndrome (generalized rash with blisters and peeling of the skin, which mainly affects genital, oral, and trunk areas), acute generalized exanthematous pustulosis (generalized scaly red rash with bumps under the skin and blisters, accompanied by fever, mainly located in skin folds, trunk, and upper limbs) and toxic epidermal necrolysis (generalized rash with blisters and peeling of the skin, particularly around the mouth, nose, eyes, and genitals, causing generalized skin peeling (more than 30% of the body surface) flu-like symptoms with skin rash, fever, gland inflammation, and abnormal blood test results (such as increased white blood cells (eosinophilia) and elevated liver enzymes) [drug reaction with eosinophilia and systemic symptoms (DRESS)] acne. If this type of reaction occurs, treatment with clarithromycin should be immediately discontinued and a doctor should be consulted to establish appropriate treatment.

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

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

- Laboratory tests: increase in the international normalized ratio (calculation to detect blood coagulation), prolongation of prothrombin time (indicates a deficit in blood coagulation) and abnormal urine color.

Specific Adverse Effects

Phlebitis at the injection site, pain at the injection site, pain at the venous puncture site, and inflammation at the injection site are specific to the intravenous formulation of clarithromycin.

After the marketing of the medicine, reports of effects on the central nervous system (e.g., somnolence and confusion) have been received with the simultaneous use of clarithromycin and triazolam. Patient monitoring is recommended.

In some reports of rhabdomyolysis, clarithromycin was administered concomitantly with statins, fibrates, colchicine, or allopurinol (see Do not take clarithromycinand Warnings and precautions).

There have been rare reports that prolonged-release clarithromycin tablets appear in the feces; many of these cases have occurred in patients with gastrointestinal anatomical disorders [including ileostomy or colostomy (surgery to expel intestinal waste artificially from the ileum or colon)] or functional disorders (caused by a defect in the body) with shortened gastrointestinal transit time. In several reports, tablet residues have appeared in the context of diarrhea. It is recommended that patients who present with tablet residues in the feces and who do not experience any improvement change to another clarithromycin formulation (e.g., suspension) or to another antibiotic.

Adverse Effects in Children and Adolescents

It is expected that the frequency, type, and severity of adverse reactions in children will be the same as in adults.

Immunocompromised Patients

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

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

In these immunocompromised patients, around 2% to 3% who received 1,000 mg or 2,000 mg of clarithromycin daily presented seriously abnormal elevated transaminase levels, as well as abnormally low white blood cell and platelet counts. A smaller percentage of patients in both dosage groups had increased blood levels of urea (which may indicate decreased renal function). In patients who received 4,000 mg daily, slightly higher incidences of abnormal values were observed in all parameters, except for the white blood cell count.

Contact a doctor as soon as possible if you experience a severe skin reaction: a red and scaly rash with bumps under the skin and blisters (pustular exanthematous). The frequency of this adverse effect is considered unknown (cannot be estimated from the available data).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is an adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Medicines and Healthcare Products Agency (AEMPS) http://www.aemps.es/. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Clarithromycin Kern Pharma

Keep this medicine out of sight and reach of children.

Do not store above 30°C.

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 thrown down the drain or into the trash. Deposit the packaging and medicines you no longer need at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Clarithromycin Kern Pharma

• The active ingredient is clarithromycin. Each coated tablet contains 500 mg of clarithromycin.
• The other components (excipients) are: pregelatinized cornstarch, sodium croscarmellose, povidone K 25, microcrystalline cellulose, anhydrous colloidal silica, magnesium stearate, hydroxypropyl methylcellulose, titanium dioxide (E-171), talc, and propylene glycol (E 1520).

Appearance of the Product and Package Contents

Clarithromycin Kern Pharma is presented in the form of coated tablets in packages with 14 or 21 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Kern Pharma, S.L.

Venus, 72 - Pol. Ind. Colón II

08228 Terrassa - Barcelona

Spain

Date of the Last Revision of this Prospectus:February 2024

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.es/.