CLARITHROMYCIN UNIDIA KERN PHARMA 500 mg MODIFIED-RELEASE TABLETS

2. What you need to know before you take Claritromicina Unidia Pharma

Do not take Claritromicina Unidía Kern Pharma

• If you are allergic to clarithromycin, 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 or liver problems.
• If you are taking ergotamine or dihydroergotamine or using 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 serious 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), ivabradine, or ranolazine (for angina pectoris or to reduce the risk of heart attack or stroke).

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

• If you are undergoing treatment with midazolam oral (for anxiety or to help fall asleep)
• If you have abnormally low levels of potassium or magnesium in your blood (hypokalemia or hypomagnesemia).

If you or a family member have a history of heart rhythm disorders (ventricular arrhythmia, including Torsade de Pointes) or abnormalities in the electrocardiogram (ECG, electrical recording 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 are taking ergotamine or dihydroergotamine or using ergotamine inhalers for migraine while taking clarithromycin.

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., 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) and clarithromycin may lower blood sugar levels too much. Careful monitoring of blood sugar is recommended.
• If you are taking a medication called warfarin or other anticoagulants, 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 medication to children under 12 years of age.

Elderly patients

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

Other medications and Claritromicina Unidía Kern Pharma

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medications, including those obtained without a prescription.

Do not take Claritromicina Unidía Kern Pharma with ergot alkaloids, astemizole, terfenadine, cisapride, domperidone, pimozide, ticagrelor, ranolazine, colchicine, certain medications for high cholesterol, and medications known to cause serious heart rhythm disturbances.

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 other anticoagulants 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 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 HIV treatment) may increase clarithromycin levels. The combination of atazanavir, etravirine, and saquinavir (also antiviral medications used in HIV treatment) 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 overactive bladder symptoms). 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 serious adverse reactions affecting the heart.
• Corticosteroids, administered orally, by injection, or inhaled (used to suppress the immune system; this is useful in treating a wide range of diseases).

Taking Claritromicina Unidía Kern Pharma with food and drinks

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

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.

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

Claritromycin passes into breast milk, so breastfeeding should be interrupted during treatment with clarithromycin.

Driving and using machines

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

Claritromicina Unidía Kern Pharma contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Claritromicina Unidia Kern Pharma

Claritromicina is administered orally.

Follow your doctor's instructions for administration of clarithromycin exactly. Consult your doctor or pharmacist if you have any doubts.

Adults, adolescents from 12 to 18 years, and children over 12 years:the 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 the treatment of community-acquired pneumonia and sinusitis, which require 6 to 14 days of therapy.

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

Do not crush or chew the clarithromycin tablets.

Take the clarithromycin tablets always with food and with a glass of water. Remember to take your medication. 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 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 discontinued 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% reduction in dosage should be implemented, resulting in a maximum dose of one clarithromycin modified-release tablet per day.

If you take more Claritromicina 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 eliminate the clarithromycin that your body has not yet absorbed. Hemodialysis or peritoneal dialysis is not effective.

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

If you forget to take Claritromicina Unidía Kern Pharma

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

If you stop taking Claritromicina Unidía Kern Pharma

Do not stop treatment early, as your illness could worsen or reappear. If you have any other questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, Clarithromycin Unidía Kern Pharma can cause adverse effects, although not all people suffer from them.

Adverse effects are classified as 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), and of unknown frequency (cannot be estimated from available data).

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.

Summary of Adverse Effects

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

• Very frequently (may affect more than 1 in 10 patients, with the intravenous injection formulation): phlebitis (inflammation of the vein) at the injection site.
• With all medications containing clarithromycin, the following have been observed frequently (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).
• Less frequently (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 (premature beat with respect to 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), 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 patch, 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 serum 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 (frequency cannot be determined from available data) the following have been observed:

• Infections: pseudomembranous colitis (diarrhea that can become severe), erysipelas (redness of the skin of variable extent 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).
• Metabolism: decrease in blood glucose concentration.
• Psychiatric disorders: psychotic disorder, confusion, depersonalization, depression, disorientation, hallucinations, daydreaming (attenuated perceptions of external stimuli).
• Nervous system: convulsions, decrease or loss of sense of taste, alteration of sense of smell, loss or decrease of sense 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, mainly affecting 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 body surface area) flu-like symptoms with skin rash, fever, gland inflammation, and abnormal blood test results (such as increased leukocytes (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 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 renal tubules).
• Laboratory tests: increase in 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 venipuncture site, and inflammation at the injection site are specific to the intravenous formulation of clarithromycin.

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

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

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 formulation of clarithromycin (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 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 those caused by the disease or by other diseases that the patient may have along with AIDS.

In adult patients treated with daily total 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, respiratory difficulty, insomnia, and dry mouth appeared. The incidences were similar in patients treated with 1,000 mg and 2,000 mg, but in general were 3 to 4 times more frequent in those who received a daily total dose of 4,000 mg of clarithromycin.

In these patients with a damaged immune system, around 2% to 3% who received 1,000 mg or 2,000 mg of clarithromycin daily presented severely 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 nitrogen (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 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 available data).

Reporting of Adverse Effects

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

5. Conservation of Clarithromycin Unidia Kern Pharma

Keep out of sight and reach of children.

No special storage conditions are required.

Do not use this medication 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 medications 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 medications you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Clarithromycin 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, hypromellose phthalate, lactose monohydrate, talc, and opadry II yellow (hypromellose, lactose monohydrate, polyethylene glycol, quinoline yellow, aluminum lake, titanium dioxide).

Appearance of the Product and Package Contents

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

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 medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.es/