Prospect: information for the user

Claritromycin Altan 500 mgLiofilized for solution for infusion EFG

1.What is Claritromycin Altan 500 mg and for what it is used

2.What you need to know before starting to use Claritromycin Altan 500 mg

3.How to use Claritromycin Altan 500 mg

4.Possible adverse effects

5.Storage of Claritromycin Altan 500 mg

6. Contents of the package and additional information

Claritromicina is an antibiotic belonging to a group of substances known as macrolides. Antibiotics interrupt the growth of bacteria (germs) that cause infections.

Claritromicina is indicated whenever parenteral therapy is required for the treatment of infections caused by susceptible organisms in adults and adolescents (12 years and older) in the following conditions:

• Pharyngitis (throat infection causing sore throat) or streptococcal tonsillitis (angina infection): only in cases where first-line treatment with beta-lactams is not possible or when sensitivity ofStreptococcus pyogenesto claritromicina has been shown.
• Acute bacterial sinusitis (infection of the paranasal sinuses around the forehead, cheeks, and eyes) (adequately diagnosed)
• Community-acquired pneumonia (inflammation of the lungs caused by various germs and originating outside a hospital).
• Acute exacerbation of chronic bronchitis (prolonged or recurring inflammation of the lungs).
• Mild to moderate skin and soft tissue infections when beta-lactam antibiotics are not suitable.

Do not useClaritromicina Altan 500 mg

• if you are allergic (hypersensitive) to clarithromycin or to other macrolide antibiotics such as erythromycin or azithromycin or to any of the other ingredients of this medicine (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 or liver problems.
• if you are taking ergotamine or dihydroergotamine or using inhalers of ergotamine for migraine while taking clarithromycin. Consult your doctor for advice or alternative medications.
• if you are taking medications called terfenadine, astemizol (allergy or hay fever medication), cisapride or domperidone (used for stomach problems) or pimozide (used to treat certain psychiatric disorders) as taking these medications with clarithromycin may cause severe heart rhythm disturbances. Consult your doctor for advice on 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 ranolazine (for angina).
• if you are taking other medications that are known to cause severe heart rhythm disturbances.
• if you are taking midazolam oral (for anxiety or to help you fall asleep)
• if you have abnormally low levels of potassium or magnesium in your blood (hypokalemia or hypomagnesemia).
• if you or a family member has a history of heart rhythm disorders (ventricular arrhythmia, including Torsade de Pointes) or abnormal electrocardiogram (ECG, heart electrical recording) called “prolongation of QT syndrome”.
• if you are taking medications called lovastatin or simvastatin (to lower cholesterol levels), as the combination of these medications may increase the risk of adverse effects. Consult your doctor for advice on alternative medications.
• if you are taking colchicine (for gout)
• if you are taking a medication called lomitapida.

Warnings and precautions

Consult your doctor or pharmacist before starting to receive Claritromicina Altan 500 mg

• 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 medications (medications to lower blood sugar such as nateglinide, pioglitazone, rosiglitazone and repaglinide, sulfonylureas or insulin) and clarithromycin may lower blood sugar too much. Careful monitoring of blood glucose is recommended.
• if you are taking a medication called warfarin or any other anticoagulant (e.g. 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 apply to you, consult your doctor before receiving clarithromycin.

Use of Claritromicina Altan 500 mg 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.

• Do not use Claritromicina Altan 500 mg with ergot alkaloids, astemizol, terfenadine, cisapride, domperidone, ivabradina, pimozide, ticagrelor, ranolazine, colchicine, certain medications for high cholesterol and medications known to cause severe heart rhythm disturbances (see Do not use Claritromicina Altan 500 mg).

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 such as dabigatran, rivaroxaban, apixaban or 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).
• Prednisolone (a corticosteroid).
• Ibrutinib or vinblastine (for cancer treatment).
• Cyclosporin (immunosuppressant).
• Rifabutin (for the treatment of certain infections).
• Tacrolimus or sirolimus (for organ transplants and severe eczema).
• Sildenafil, tadalafil or vardenafil (to treat erectile dysfunction in adult men or for pulmonary hypertension (high blood pressure in the blood vessels of the lungs)).
• Zidovudine (for viruses).
• St. John's Wort (herbal product for depression).
• Phenobarbital (medication for epilepsy).
• Nevirapine and efavirenz may decrease clarithromycin levels.
• Rifampicin or rifapentine (for tuberculosis treatment).
• Omeprazole (for stomach acid and ulcers).
• Ritonavir (antiviral medication used in HIV treatment) may increase clarithromycin levels. Taking 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 both medication levels.
• Fluconazole, another antifungal, may increase clarithromycin levels.
• Tolterodine (for overactive bladder symptoms). In some patients, tolterodine levels may increase when taken with clarithromycin.
• Quetiapine (for schizophrenia or other psychiatric conditions).

Macrolide antibiotics (certain penicillins and cephalosporins)

• Aminoglycosides (used as antibiotics to treat infections).
• Calcium channel blockers (medications for high blood pressure).
• Hydroxychloroquine or chloroquine (used to treat conditions such as rheumatoid arthritis, or to treat or prevent malaria). Taking these medications with clarithromycin may increase the risk of abnormal heart rhythms and other severe adverse effects 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 range of diseases).

Pregnancy, lactation and fertility

If you are pregnant or breastfeeding, or 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 risks, 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.

Claritromicina Altan 500 mg lyophilized for solution for infusion contains sodium

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

Claritromicina is administered intravenously.

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

The recommended daily dose of intravenous claritromicina 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 claritromicina treatment when your doctor indicates.

In patients with renal insufficiency and a creatinine clearance of less than 30 ml/min, the claritromicina 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.

Claritromicina intravenous should not be administered as a bolus injection or by intramuscular route.

Use in children and adolescents:

Children (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.

If you use moreClaritromicina Altan 500 mg than you should

If you use more Claritromicina Altan than you should, you can expect gastrointestinal disturbances and consult your doctor or pharmacist immediately, as they will try to quickly eliminate the claritromicina that your body has not yet absorbed. Hemodialysis or peritoneal dialysis are not effective.

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

If you forgot to useClaritromicina Altan 500 mg

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 withClaritromicina Altan500 mg

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

Like all medications, this medication may cause side effects, although not everyone will experience them.

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

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

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

Summary of side effects

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

? Very common (may affect more than 1 in 10 patients, with the intravenous formulation): phlebitis (inflammation of the vein) at the injection site.

? With all clarithromycin-containing medications, the following have been observed with common (may affect up to 1 in 10 patients) frequency:

- Digestive system: diarrhea, vomiting, gastroenteritis that hinders digestion (dyspepsia), nausea, abdominal pain.

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

- Skin: mild skin eruptions, excessive sweating.

- Psychiatric disorders: insomnia.

- Vascular disorders: vasodilation.

- Liver disorders: abnormal liver function tests.

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

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

- Infections: cellulitis (only with the intravenous formulation), candidiasis (infection by a type of fungus), vaginal infection.

- Blood abnormalities: decreased white blood cell count.

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

- Nutritional disorders: anorexia, decreased appetite.

- Psychiatric disorders: anxiety.

- Nervous system: loss of consciousness and difficulty moving (both effects, only with the intravenous 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 formulation), prolongation of the QT interval (electrocardiogram indicator of possible ventricular arrhythmias), extrasystoles (premature heartbeat, only with the intravenous formulation), palpitations (alterations in heartbeats).

- Respiratory disorders: asthma (difficulty breathing, chest oppression, and nocturnal or morning cough, only with the intravenous formulation), pulmonary embolism (blockage of the pulmonary artery causing chest pain on one side, cough, and difficulty breathing, only with the intravenous formulation).

- Gastrointestinal disorders: esophagitis (inflammation of the esophagus, only with the intravenous formulation), gastroesophageal reflux disease (damage to the esophagus causing burning sensation, chronic cough, inflammation of the stomach mucosa (gastritis), inflammation of the oral mucosa, inflammation of the tongue, constipation, dry mouth, belching, flatulence.

- Liver disorders: increased alanine aminotransferase (liver enzyme), increased aspartate aminotransferase (another liver enzyme).

- Skin: dermatitis bullous (vesicular eruptions, only with the intravenous formulation), pruritus, urticaria (edematous, red, and itchy skin lesions).

- Muscular disorders: musculoskeletal rigidity (only with the intravenous formulation).

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

- Laboratory tests: abnormal albumin-globulin ratio (only with the intravenous formulation).

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

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

- Blood abnormalities: decreased neutrophil count (a type of white blood cell), decreased platelet count.

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

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

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

- Ear: deafness.

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

- Vascular disorders: hemorrhage.

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

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

- Skin: Stevens-Johnson syndrome (generalized eruption with blisters and skin peeling, mainly affecting 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), systemic symptoms such as fever, glandular inflammation, and abnormal blood tests (such as eosinophilia and elevated liver enzymes) [drug reaction with eosinophilia and systemic symptoms (DRESS)], acne. If these types of reactions occur, discontinue clarithromycin treatment immediately and consult a doctor to initiate appropriate treatment.

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

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

- Laboratory tests: increased international normalized ratio (calculation to detect blood coagulation), prolonged prothrombin time (indicates a deficiency in blood coagulation), 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. It is suggested to monitor the patient.

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

Side effects in children and adolescents:

Studies have been conducted with clarithromycin pediatric suspension 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 effects 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 total daily doses of 1,000 mg and 2,000 mg of clarithromycin, the most common adverse reactions that appeared were: nausea, vomiting, taste alteration, abdominal pain, diarrhea, skin rash, flatulence, headache, constipation, hearing abnormalities, and elevated transaminases (which may indicate liver, pancreas, heart, or muscle damage). With lower frequency, difficulty breathing, insomnia, and dry mouth appeared. The incidence was similar in patients treated with 1,000 mg and 2,000 mg, but in general, it was 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 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 incidence of abnormal values in all parameters, except white blood cell count, was observed.

Consult a doctor as soon as possible if you experience a severe skin reaction: a red, scaly eruption with subcutaneous nodules and blisters (pustulosis 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 System for 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 medication.

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Keep out of the reach and sight of children.

This medication does not require special storage conditions..

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

Do not useClaritromycinafter the expiration date appearing on the packaging or on the vial label.The expiration date is the last day of the month indicated.

Medications should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

Composition of ClarithromycinAltan500 mg

- The active ingredient is clarithromycin 500 mg.

- The other components are lactobionic acid, sodium hydroxide, and water for injection.

Aspect of the product and content of the package

Sediment or powder for infusion solution of white to almost white color in a glass vial.

Package sizes: 1 vial, 6 vials, and 100 vials.

Not all package sizes may be marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Altan Pharmaceuticals, S.A.

C/ Cólquide 6, Portal 2, 1st Floor, Prisma Building. Office F.

28230 Las Rozas (Madrid)

Responsible for manufacturing

Altan Pharmaceuticals, S.A.

Avda. de la Constitución 198-199, Monte Boyal Industrial Estate,

45950 Casarrubios del Monte (Toledo) Spain

This leaflet has been reviewed in December 2023

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

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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 dilution with an appropriate intravenous diluent, over a period of 60 minutes. There are no data to justify the use of intravenous clarithromycin in children. Clarithromycin should not be administered by bolus injection or intramuscularly.

Older patients:

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 at the discretion of the doctor.

Renal insufficiency:

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

In adolescents (12 to 18 years of age), the dose is the same as in adults.

Instructions for reconstitution and dilution of the medication before administration

Before administration, the product should be visually inspected to check for the absence of particles and discoloration. For single use only. Any unused solution for injection should be discarded.

1. Prepare the initial solution of clarithromycin I.V by adding 10 ml of sterile water for injection to the vial. Only use sterile water for injection, as other diluents may cause precipitation during reconstitution. Do not use diluents containing preservatives or inorganic salts.

Considering the stability studies in use performed with sterile water, the product is stable for 24 hours at room temperature (25°C) and 48 hours in the refrigerator (5°C).

1. The reconstituted product (500 mg in 10 ml of water for injection) before administration should be added to a minimum of 250 ml of one of the following diluents:

The final reconstituted product should be used within 24 hours if stored at room temperature (25°C) or within 48 hours if stored in the refrigerator (5°C).

No other medications or chemical agents should be added to the final mixture unless their effect on the physical and chemical stability of the solution has been determined.

From a microbiological point of view, the diluted product should be used immediately. If not used immediately, the storage times in use and the conditions before use are the responsibility of the user/administrator and should not normally exceed 24 hours at 2-8°Cunless the dilution was performed in aseptic conditions and validated.

No other medications or chemical agents should be added to the final mixture, unless their effect on the 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 initiated.

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.