PATIENT INFORMATION LEAFLET

KLACID 500 mg lyophilized powder for infusion

Clarithromycin

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

• Keep this leaflet, as you may need to read it again.

• If you have any questions, consult your doctor, pharmacist or nurse.

• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

Klacid 500 mg lyophilized is an antibiotic belonging to a group of substances called macrolides. Antibiotics interrupt the growth of bacteria (germs) that cause infections.

Klacid 500 mg lyophilized is indicated whenever parenteral therapy is required for the treatment of infections caused by sensitive organisms in adults 18 years of age and older, in the following conditions:

- Pharyngitis (infection of the pharynx that causes sore throat) or streptococcal tonsillitis (infection of the tonsils) : only in cases where it is not possible to treat with first-line beta-lactam antibiotics or when sensitivity of Streptococcus pyogenes to clarithromycin has been shown.

- Acute bacterial sinusitis (infection of the paranasal sinuses located around the forehead, cheeks, and eyes) (adequately diagnosed).

- Community-acquired pneumonia (inflammation of the lungs caused by different germs and originating outside a hospital).

- Acute exacerbation of chronic bronchitis (acute worsening of chronic inflammation of the lungs) .

- Skin and soft tissue infections of mild to moderate severity when beta-lactam antibiotics are not appropriate. .

No use Klacid 500 mg liofilizado for solution for infusion

• If you are allergic to clarithromycin, other macrolide antibiotics such as erythromycin or azithromycin, or to any of the other components of this medication (including those 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 domperidone (used for stomach problems) or pimozida (medication 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 pectoris).
• If you are taking other medications that are known to cause severe heart rhythm disturbances.
• If you are being treated with midazolam oral (for anxiety or to help fall asleep)
• If you have abnormally low levels of potassium or magnesium in your blood (hypopotasemia or hypomagnesemia).
• If you or a family member has a history of heart rhythm disorders (ventricular arrhythmia, including Torsade de Pointes) or abnormalities in the 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 a medication with lomitapida

Warnings and precautions

Consult your doctor or pharmacist before starting to receive Klacid

• If you have heart, kidney, or liver problems.
• If you have or are prone to fungal infections (for example, 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 such as nateglinida, pioglitazona, rosiglitazona, and repaglinida, sulfonilureas, or insulin) and clarithromycin may lower blood sugar too much. Careful monitoring of blood sugar is recommended.
• If you are taking a medication called warfarin (blood thinner).
• 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 receiving clarithromycin.

Use of Klacid 500 mg liofilized for solution for infusion with other medications

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.

Klacid should not be used with ergotamine alkaloids, astemizol, terfenadine, cisaprida, domperidone, pimozida, ticagrelor, ranolazina, colchicine, certain medications for high cholesterol, and medications known to cause severe heart rhythm disturbances (see Do not use Klacid).

This is especially important if you are taking medications for:

Or if you are taking any medication called:

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 need to weigh the benefits against the potential risk, especially during the first three months of pregnancy.

Clarithromycin 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.

Klacid 500 mg liofilized for solution for infusion contains sodium

This medication contains less than 23 mg of sodium (1 mmol) per vial; this is essentially "sodium-free"

Klacid 500 mg lyophilized is administered intravenously.

Follow exactly the administration instructions for Klacid 500 mg lyophilized as indicated by your doctor. In case of doubt, consult your doctor, pharmacist, or nurse again.

The recommended daily dose of intravenous clarithromycin for adults 18 years of age and older is 1 g, divided into two equal doses and infused over a period of 60 minutes after proper dilution.

Treatment can be administered for 2-5 days, and should be changed to oral clarithromycin treatment when your doctor indicates.

In patients with renal insufficiency and a creatinine clearance of 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 discontinued after 14 days.

Clarithromycin intravenous should not be administered by bolus injection or intramuscularly.

Use in children and adolescents

Children and adolescents (under 12 years) should not use this medication. Your doctor will prescribe another suitable medication for your child.

For adolescents 12 to 18 years of age, the same dose as in adults is used.

Appropriate presentations for children from 6 months and adolescents under 12 years are: Klacid 25 mg/ml granulated for oral suspension and Klacid 50 mg/ml granulated for oral suspension.

If you use more Klacid 500 mg lyophilized for solution for infusion than you should

If you use more Klacid 500 mg lyophilized than you should, gastrointestinal disturbances may be expected, and you should immediately consult your doctor or pharmacist, who 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 the Toxicological Information Service, phone 91.562.04.20, indicating the medication and the amount ingested.

If you forgot to use Klacid 500 mg lyophilized for infusion

If you think you may have forgotten a dose, consult your doctor or nurse. Do not administer a double dose to compensate for the missed doses.

If you interrupt treatment with Klacid 500 mg lyophilized for solution for infusion

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

Like all medicines, this medicine can 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 altered taste. These adverse reactions are usually mild in intensity 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 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 (may affect up to1 in 10 patients) frequency:

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

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

- 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).

?Uncommon (may affect up to1 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, 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).

- 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 intravenous formulation), dizziness, somnolence, tremors.

- Ear and balance: vertigo, hearing problems, ringing in the ears.

- Heart disorders: cardiac arrest and altered heart rhythm (fibrillation auricular) (both effects, only with intravenous formulation), prolonged QT interval (indicator of electrocardiogram that arrhythmias may occur), 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: esophageal inflammation (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), stomach mucosa inflammation, 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 to the intestine and liver inflammation (hepatitis) (both effects, only with immediate-release tablets), increased alanine aminotransferase (liver enzyme), increased aspartate aminotransferase (another liver enzyme), and increased gamma-glutamyltransferase (another liver enzyme, only with immediate-release tablets).

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

- Muscular 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 poor 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 blood (both effects, 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 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 (swelling under the skin).

- Psychiatric disorders: psychotic disorder, confusion, depersonalization, depression, disorientation, hallucinations, and somnambulism (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 acorchamiento 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), discoloration of the tongue, discoloration of the teeth.

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

- Skin: Stevens-Johnson syndrome (generalized eruption with blisters and skin peeling, affecting mainly genital, oral, and trunk areas), generalized acute exanthematous pustulosis (generalized scaly eruption with red color, with subcutaneous nodules and blisters, accompanied by fever, mainly 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 genitals, causing generalized skin peeling (more than 30% of body surface area) and symptoms of flu-like with skin eruption, fever, glandular inflammation, and abnormal blood test results (such as increased leukocytes (eosinophilia) and elevated liver enzymes) [drug reaction with eosinophilia and systemic symptoms (DRESS)], acne.In the event of these reactions, discontinue clarithromycin treatment immediately and consult your doctor to establish an appropriate treatment.

- Muscular 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 (indicating a coagulation disorder), and abnormal urine color.

Specific side 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 marketing, reports have been received of effects on the central nervous system (e.g., somnolence and confusion) with the simultaneous use of clarithromycin and triazolam. Monitor the patient.

In some of the reports of rhabdomyolysis, clarithromycin was administered concomitantly with statins, fibrates, colchicine, or allopurinol (seeDo not take Klacid 500 mg lyophilized for solution for infusionandWarnings and precautions).

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

Side effects in children and adolescents:

Clarithromycin pediatric suspension has been studied in clinical trials in children aged 6 months to 12 years. Therefore, children under 12 years should take the pediatric suspension of clarithromycin. There are no sufficient data to recommend a dosing regimen for the intravenous formulation of clarithromycin in patients under 18 years.

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 in 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 adverse reactions possibly associated with clarithromycin administration from those caused by the disease or other diseases that the patient may have with 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, altered taste, abdominal pain, diarrhea, skin rash, flatulence, headache, constipation, hearing abnormalities, and elevated transaminases (which may indicate liver, pancreas, heart, or muscle damage). With lesser frequency, 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 blood urea nitrogen levels (which may indicate decreased renal 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 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 System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

No special storage conditions are required.

• • Reconstituted solution (500 mg in 10 ml of water for injectable preparations): can be stored for 24 hours at 25°C and for 48 hours at 2°C-8°C.
• The final reconstituted solution (reconstituted infusion solution added to 250 ml of diluent, respectively for each diluent mentioned) can be stored for 6 hours at room temperature (25°C) or for 48 hours in the refrigerator (2°C-8°C).

Do not use Klacid 500 mg lyophilized 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. If in doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need. In this way, you will help protect the environment.

Composition ofKlacid 500 mg lyophilizedfor solution for infusion

The active ingredient of Klacid 500 mg lyophilized is clarithromycin. Each vial contains 739.5 mg of clarithromycin lactobionate, equivalent to 500 mg of clarithromycin.

The other components are: lactic acid and sodium hydroxide (for pH adjustment).

Aspect of the product and contents of the package

White or off-white lyophilized powder in the form of a cake with a light aromatic odor in a glass vial. Each package contains 1 vial of 15 ml.

Holder of the marketing authorization and responsible for manufacturing

Holder:

Viatris Healthcare Limited

Damastown Industrial Park

Mulhuddart, Dublin 15

Dublin

Responsible for manufacturing:

Delpharm Saint Remy

Rue de l´Isle

28380 Saint-Remy-sur-Avre

France

Further information about this medicinal product can be obtained by contacting the local representative of the holder of the marketing authorization:

Viatris Pharmaceuticals, S.L.

C/ General Aranaz, 86

28027 - Madrid

Spain

Date of the last review of this leaflet: March 2024

“Detailed information about this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/”

-----------------------------------------------------------------------------------------------------------------

INFORMATION FOR HEALTHCARE PROFESSIONALS:

Adults:

The recommended dose in adults of 18 years or older is 1 g per day, divided into two equal doses, each infused after a posterior dilution with an appropriate intravenous diluent, for a period of 60 minutes. There are no data to justify the intravenous use of clarithromycin in children. Clarithromycin should not be administered by bolus injection or intramuscularly.

Older adults:

The same dose as adults.

Posology in patients with mycobacterial infections:

Although there are currently no data related to the use of intravenous clarithromycin in immunocompromised patients, there are data on the use of oral clarithromycin in HIV-infected patients. In disseminated or localized infections (M. avium, M. intracellulare, M. chelonae, M. fortuitum, M. kansasii), the recommended treatment in adults is 1000 mg/day divided into two doses.

The intravenous treatment can be administered for 2-5 days in severely ill patients and should be changed to oral clarithromycin treatment as soon as possible, as indicated by the doctor.

Renal insufficiency:

In patients with renal insufficiency, who have a creatinine clearance of less than 30 ml/min, the dose of clarithromycin should be reduced to half of the recommended dose.

Liver insufficiency:

Clarithromycin should not be administered to patients with severe liver insufficiency combined with renal insufficiency. (see section 4.3)

Pediatric population:

There are not enough data to recommend a dosing regimen for the intravenous formulation of clarithromycin in patients under 18 years old.

Instructions for preparation/manipulation

1. Prepare the initial solution of clarithromycin (reconstituted solution) by adding 10 ml of sterile water for injection to the 500 mg vial. Gently shake until completely dissolved without any visible undissolved macroparticles (it may take up to 5 minutes). Only sterile water for injection can be used, as other diluents may cause precipitation during reconstitution. Do not use diluents containing preservatives or inorganic salts.

Observation: When the product is reconstituted as mentioned above, each ml of the reconstituted solution contains 50 mg of clarithromycin.

The resulting solution contains an effective antimicrobial preservative. If stored at room temperature (25°C), the reconstituted product should be used within 24 hours, and if stored at 2-8°C, within 48 hours.

2. Before administration, the reconstituted solution (500 mg in 10 ml of water for injection) should be added to 250 ml of the following diluents:

. Sodium chloride 0.9%.

. Glucose 5%.

. Glucose 5% in sodium chloride 0.3%.

. Glucose 5% in sodium chloride 0.45%.

. Glucose 5% in Lactate Ringer solution or

. Lactate Ringer solution

The final diluted solution (the reconstituted solution to which 250 ml of the mentioned diluents have been added) can be stored for 6 hours at room temperature (25°C) or for 48 hours in the refrigerator (2-8°C).

No other medications or chemical agents should be added to the final mixture, unless their effect on physical or chemical stability has been demonstrated.

Pharmaceutical incompatibilities

None have been described.

Overdose

In case of overdose, treatment should be interrupted and appropriate supportive measures should be instituted.

The adverse reactions accompanying overdose should be treated by rapid elimination of the non-absorbed drug and supportive measures.

It is not expected that clarithromycin levels will be significantly affected by hemodialysis or peritoneal dialysis.