CLARITHROMYCIN VIR 500 mg FILM-COATED TABLETS

2. What you need to know before you take Claritromicina Vir

Do not take Claritromicina Vir:

• 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 and 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 diseases) 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).
• If you are taking other medications that are known to cause serious heart rhythm disturbances.
• If you are undergoing treatment with oral midazolam (for anxiety or to help fall asleep).
• If you have abnormally low levels of potassium (electrocardiogram alterations) or magnesium in the blood (hypokalemia or hypomagnesemia).
• If you or a family member have a history of heart rhythm disorders (ventricular cardiac arrhythmia, including Torsades de Pointes) or electrocardiogram (ECG) abnormalities 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.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Claritromicina Vir:

• If you have heart, kidney, or liver problems.
• If you have or are prone to fungal infections (such as 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 meglitinides) and clarithromycin may lower blood sugar levels too much. Careful glucose monitoring is recommended.
• If you are taking a medication called warfarin (blood anticoagulant).
• 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 Vir

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medications, 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 serious heart rhythm disturbances. See Do not take Claritromicina Vir.

This is especially important if you are taking medications for:

• Heart problems (such as digoxin, verapamil, quinidine, or disopyramide).
• Blood thinning (such as warfarin).
• Migraine (such as ergotamine or dihydroergotamine).
• Epilepsy or bipolar disorder (carbamazepine, valproate, phenobarbital, or phenytoin).
• High cholesterol (such as 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 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).
• Warfarin or other anticoagulants, such as dabigatran, rivaroxaban, apixaban, edoxaban (for blood thinning).
• Hydroxychloroquine or chloroquine (used for treating diseases such as rheumatoid arthritis, or for treating or preventing 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 the treatment of a wide variety 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.

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.

Claritromicina passes into 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 caution when driving or using hazardous machinery.

Claritromicina Vir contains propylene glycol

This medicine contains 2.610 mg of propylene glycol in each tablet.

3. How to take Claritromicina Vir

Claritromicina Vir is administered orally.

Follow the administration instructions of the medication indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Adults and children over 12 years:

Patients with respiratory tract, skin, and soft tissue infections:

The usual 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.

Helicobacter pylori eradication in patients with duodenal ulcers (adults):

In patients with peptic ulcer associated with Helicobacter pylori, the recommended treatments are:

Triple therapy: one 500 mg tablet of clarithromycin twice a day, with 30 mg of lansoprazole twice a day and 1000 mg of amoxicillin twice a day for 10 days.

or one 500 mg tablet of clarithromycin with 1000 mg of amoxicillin and 20 mg of omeprazole, all administered twice a day, for 7 to 10 days.

Elderly patients

As for adults.

Patients with mycobacterial infections:

The recommended average dose for the prevention and treatment of mycobacterial infections is one 500 mg tablet 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 discontinued after 14 days.

Since the tablet cannot be halved, the daily dose cannot be less than 500 mg/day, so Claritromicina Vir 500 mg should not be administered in this group of patients. There is Claritromicina Vir 250 mg for administration in this group of patients.

Follow these instructions unless your doctor has given you different instructions. Remember to take your medication. Take the tablets at the same time every day.

Your doctor will indicate the duration of your treatment.

Use in children and adolescents

Claritromicina Vir 500 mg is not suitable for children and adolescents under 12 years of age.

If you think the effect of Claritromicina Vir is too strong or too weak, consult your doctor or pharmacist.

If you take more Claritromicina Vir than you should

If you have taken more Claritromicina Vir 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 is not effective.

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 medication and the amount ingested.

If you forget to take Claritromicina Vir

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 Vir

Do not stop treatment before, as even if you are already feeling better, your illness could worsen or reappear. If you have any other questions about the use of this medication, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine 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, in both 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 patient population 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 formulation): phlebitis (inflammation of the vein) at the injection site.
• Frequently (may affect up to 1 in 10 patients) with all medicines containing clarithromycin, the following have been observed:

• 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 rash, excessive sweating.
• Psychiatric disorders: insomnia.
• Vascular disorders: dilation of blood vessels in the body (vasodilation).
• Liver disorders: abnormal liver function tests.
• Disorders at the injection site: pain and inflammation at the injection site (only with the intravenous formulation).

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

• Infections: cellulitis (only with the intravenous 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 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 formulation), dizziness, drowsiness, 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 formulation), prolongation of the QT interval (indicator of the electrocardiogram that may produce ventricular arrhythmias), extrasystoles (premature heartbeat, only with the intravenous formulation), palpitations (alterations in heartbeats).
• Respiratory disorders: asthma (difficulty breathing, chest oppression, and nocturnal or early morning cough, only with the intravenous 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 formulation).
• Gastrointestinal disorders: esophagus inflammation (only with the intravenous 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 eruptions, only with the intravenous 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 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 formulation).
• General disorders: discomfort (only with immediate-release tablets), chest pain, chills, and fatigue (the last three, only with immediate-release tablets).
• Laboratory analysis: abnormal albumin-globulin ratio (only with the intravenous formulation), increase in serum alkaline phosphatase and increase in lactate dehydrogenase in blood (the last two, only with immediate-release tablets).

• With unknown frequency (their frequency cannot be determined with 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).
• 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 (inflammation of the pancreas), discoloration of the tongue, discoloration of the teeth.
• Liver disorders: liver failure, hepatocellular jaundice (yellowing of the skin and eyes).
• Skin: Stevens-Johnson syndrome (generalized eruption with blisters and peeling of the skin, mainly affecting the genital, oral, and trunk areas), acute generalized exanthematous pustulosis (generalized scaly red eruption with bumps under the skin and blisters, accompanied by fever, mainly located in skin folds, trunk, and upper limbs) and toxic epidermal necrolysis (generalized eruption 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 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 analysis: 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 medicine, reports of effects on the central nervous system (e.g., drowsiness and confusion) have been received with the simultaneous use of clarithromycin and triazolam. It is suggested to monitor the patient.

In some reports of rhabdomyolysis, clarithromycin was administered concomitantly with statins, fibrates, colchicine, or allopurinol; see Do not take Clarithromycin Vir and 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, 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, 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 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 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 available data).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, 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 medicine.

5. Conservation of Clarithromycin Vir

Keep this medicine out of sight and reach of children.

This medicine does not require special storage conditions.

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 away through wastewater or household waste. Deposit the packaging and medicines that you no longer need in the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Clarithromycin Vir

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

Appearance of the Product and Package Contents

Clarithromycin Vir 500 mg is presented in the form of film-coated tablets, round, white, in packages with 14, 21, and 500 tablets.

It is possible that only some package sizes are marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Industria Química y Farmacéutica VIR, S.A.

C/ Laguna 66-68-70. Polígono Industrial URTINSA II

28923 Alcorcón – Madrid

Spain

Manufacturer

KERN PHARMA, S.L.

C/ Venus, 72. Polígono Ind. Colón II

08228 Terrassa (Barcelona)

Spain

Or

Industria Química y Farmacéutica VIR, S.A.

C/ Laguna 66-68-70. Polígono Industrial URTINSA II

28923 Alcorcón – Madrid

Spain

Date of the Last Revision of this Prospectus: March 2024

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) https://www.aemps.gob.es/