Klacid 500 mg lyophilisate for solution for infusion

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

KLACID 500 mg lyophilisate for solution for infusion

Clarithromycin

Read the entire package leaflet carefully before you start using this medicine, as 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 and must not be given to other people, even if they have the same symptoms as you, since it could harm them.

• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if the effects are not listed in this leaflet. See section 4.

Contents of the package leaflet:

1. What Klacid 500 mg lyophilisate for solution for infusion is and what it is used for
2. What you need to know before using Klacid 500 mg lyophilisate for solution for infusion
3. How to use Klacid 500 mg lyophilisate for solution for infusion
4. Possible adverse effects
5. Storage of Klacid 500 mg lyophilisate for solution for infusion
6. Contents of the pack and other information

1. What KLACID 500 mg lyophilisate for solution for infusion is and what it is used for

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

Klacid 500 mg lyophilisate is indicated whenever parenteral therapy is required for the treatment of infections caused by susceptible organisms in adults and adolescents (12 to 18 years of age) under the following conditions:

• Streptococcal pharyngitis (infection of the pharynx causing sore throat) or tonsillitis: only in cases where first-line treatment with beta-lactam antibiotics is not possible, or when sensitivity of Streptococcus pyogenes to clarithromycin has been demonstrated.

• 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 various pathogens and acquired outside the hospital).

• Acute exacerbation of chronic bronchitis (worsening of long-standing or recurrent lung inflammation).

• Mild to moderate skin and soft tissue infections when beta-lactam antibiotics are not appropriate.

2. What you need to know before using Klacid 500 mg lyophilisate for solution for infusion

Do not use Klacid 500 mg lyophilisate for solution for infusion

• If you are allergic to clarithromycin, other macrolide antibiotics such as erythromycin or azithromycin, or to any of the other ingredients of this medicine (listed in section 6).
• If your creatinine clearance is 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 advice on alternative medications.
• If you are taking medicines known as terfenadine, astemizole (a medicine for hay fever or allergies), cisapride or domperidone (used for stomach problems), or pimozide (a medicine used to treat certain psychiatric conditions), as taking these with clarithromycin may cause serious disturbances in heart rhythm. 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), ivabradine, or ranolazine (for angina).
• If you are taking other medicines known to cause serious disturbances in heart rhythm.
• If you are being treated with oral midazolam (for anxiety or to help sleep).
• If you have abnormally low levels of potassium or magnesium in your blood (hypokalaemia or hypomagnesaemia).
• If you or someone in your family has a history of heart rhythm disorders (ventricular arrhythmia, including Torsade de Pointes) or abnormalities on the electrocardiogram (ECG, electrical recording of the heart) known as "QT prolongation syndrome".
• If you are taking medicines called lovastatin or simvastatin (to lower cholesterol levels), as combining these with clarithromycin 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 medicine containing lomitapide.

Warnings and precautions

Consult your doctor or pharmacist before starting Klacid

• 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 medicines known as colchicine, triazolam, midazolam (for anxiety or insomnia), lovastatin, simvastatin.
• If you are diabetic and taking hypoglycaemic agents (medicines to lower blood sugar such as nateglinide, pioglitazone, rosiglitazone, repaglinide, sulfonylureas, or insulin), as clarithromycin may excessively lower blood glucose levels. Careful monitoring of blood glucose is recommended.
• If you are taking a medicine called warfarin (a blood thinner).
• If you have myasthenia gravis, a condition in which your muscles become weak and tire easily.
• If you develop severe or prolonged diarrhoea during or after taking clarithromycin, consult your doctor immediately.

If any of these situations apply to you, consult your doctor before receiving clarithromycin.

Using Klacid 500 mg lyophilisate for solution for infusion with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription.

Klacid must not be used with ergot alkaloids, astemizole, terfenadine, cisapride, domperidone, pimozide, ticagrelor, ranolazine, colchicine, certain medicines for high cholesterol, or medicines known to cause serious disturbances in heart rhythm (see "Do not use Klacid").

This is especially important if you are taking medicines for:

• Heart problems (e.g. digoxin, verapamil, quinidine, or disopyramide).
• Thinning the blood (e.g. warfarin or other anticoagulants such as 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 medicine 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 (an immunosuppressant).

• Rifabutin (for treating certain infections).

• Tacrolimus or sirolimus (for organ transplants and severe eczema).

• Sildenafil, tadalafil, or vardenafil (to treat impotence in adult men or pulmonary arterial hypertension (high blood pressure in the blood vessels of the lung)).

• Zidovudine (to treat viruses).

• St. John’s wort (a herbal product used to treat depression).

• Phenobarbital (a medicine to treat epilepsy).

• Nevirapine and efavirenz may reduce levels of clarithromycin.

• Rifampicin or rifapentine (to treat tuberculosis).

• Omeprazole (to treat stomach acidity and stomach or intestinal ulcers).

• Ritonavir (an antiviral medicine used in the treatment of HIV infection) may increase levels of clarithromycin. Concomitant use of atazanavir, etravirine, and saquinavir (also antiviral medicines used in HIV treatment) with clarithromycin may increase levels of both atazanavir (or saquinavir) and clarithromycin.

• Itraconazole (an antifungal) taken together with clarithromycin may increase levels of both medicines.

• Fluconazole, another antifungal medicine, may increase levels of clarithromycin.

• Tolterodine (to treat symptoms of overactive bladder syndrome). In some patients, levels of tolterodine 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 (medicines to treat high blood pressure).

• Hydroxychloroquine or chloroquine (used to treat conditions such as rheumatoid arthritis, or to treat or prevent malaria). Taking these medicines together with clarithromycin may increase the risk of abnormal heart rhythms and other serious adverse effects affecting the heart.

• Corticosteroids, administered orally, by injection, or by inhalation (used to suppress the immune system; this is useful in treating a wide range of conditions).

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

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

Clarithromycin passes into breast milk, so breastfeeding should be discontinued 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 operating dangerous machinery during treatment with clarithromycin.

Klacid 500 mg lyophilisate for solution for infusion contains sodium

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

3. How to use KLACID 500 mg lyophilisate for solution for infusion

Klacid 500 mg lyophilisate is administered intravenously.

Follow exactly the administration instructions for Klacid 500 mg lyophilisate provided by your doctor. If in doubt, consult your doctor, pharmacist, or nurse again.

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

Treatment may be given for 2–5 days and should be switched to oral clarithromycin treatment as directed by your doctor.

In patients with renal impairment and a creatinine clearance of less than 30 ml/min, the clarithromycin dose should be reduced by half, i.e., 250 mg once daily, or 250 mg twice daily in more severe infections. In these patients, treatment should be discontinued after 14 days.

Intravenous clarithromycin must not be administered as a bolus injection or by intramuscular route.

Use in children and adolescents

Children and adolescents (under 12 years of age) must not use this medicine. Your doctor will prescribe another medicine suitable for your child.

For adolescents aged 12 to 18 years, the same dose as in adults should be used.

The appropriate formulations for children from 6 months of age and adolescents under 12 years of age are: Klacid 25 mg/ml granules for oral suspension and Klacid 50 mg/ml granules for oral suspension.

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

If you use more Klacid 500 mg lyophilisate than prescribed, gastrointestinal disturbances may be expected. Immediately consult your doctor or pharmacist, as they will need to rapidly eliminate any clarithromycin not yet absorbed by your body. Haemodialysis or peritoneal dialysis are not effective.

In case of overdose or accidental ingestion, contact the Toxicology Information Service at telephone number 91.562.04.20, indicating the medication and the amount ingested.

If you forget to use Klacid 500 mg lyophilisate for infusion

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

If you stop treatment with Klacid 500 mg lyophilisate for infusion solution

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Adverse effects are classified as very common (may affect more than 1 in 10 people), common (may affect up to 1 in 10 people), uncommon (may affect up to 1 in 100 people), and frequency not known (cannot be estimated from the available data).

Common and very common reactions associated with clarithromycin treatment in both adults and children are abdominal pain, diarrhoea, nausea, vomiting, and altered taste. These adverse reactions are usually mild in intensity and consistent 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 adverse effects

Adverse effects are listed in order of decreasing severity within each body system:

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

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

• Gastrointestinal system: diarrhoea, vomiting, gastric discomfort impairing digestion (dyspepsia), nausea, abdominal pain.
• Nervous system: altered taste sensation, headache, taste disturbance.
• Skin: mild skin rashes, excessive sweating.
• Psychiatric disorders: insomnia.
• Vascular disorders: dilation of blood vessels in the body (vasodilation).
• Hepatic disorders: abnormal liver function tests.
• Administration site reactions: pain and inflammation at the injection site (only with intravenous injection formulation).

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

• Infections: cellulitis (only with intravenous injection formulation), candidiasis (fungal infection), gastroenteritis (only with prolonged-release tablets), infection (only with granules for oral suspension), vaginal infection.
• Blood disorders: decreased white blood cells, decreased neutrophils (a type of white blood cell, only with immediate-release tablets), increased platelets and, to a lesser extent, increased red and white blood cells in blood (only with granules for oral suspension), increased eosinophils (a type of white blood cell, only with immediate-release tablets).
• Immune system disorders: anaphylactoid reaction (generalized allergic reaction, only with intravenous injection formulation), hypersensitivity (exaggerated allergic reaction to external agents).
• Eating disorders: anorexia, decreased appetite.
• Psychiatric disorders: anxiety and nervousness (the latter only with granules for oral suspension).
• Nervous system: loss of consciousness and difficulty moving (both effects, only with intravenous injection formulation), dizziness, somnolence, tremor.
• Ear and balance: vertigo, hearing disturbances, tinnitus.
• Cardiac disorders: cardiac arrest and irregular heart rhythm (atrial fibrillation) (both effects, only with intravenous injection formulation), QT interval prolongation (an electrocardiogram indicator of potential ventricular arrhythmias), extrasystoles (premature heartbeat compared to normal heart rate, only with intravenous injection formulation), palpitations (irregular heartbeats).
• Respiratory disorders: asthma (difficulty breathing, chest tightness, and nocturnal or early morning cough, only with intravenous injection formulation), epistaxis (only with prolonged-release tablets), pulmonary embolism (blockage of the pulmonary artery causing one-sided chest pain, cough, and breathing difficulty, only with intravenous injection formulation).
• Gastrointestinal disorders: oesophagitis (only with intravenous injection formulation), gastro-oesophageal reflux disease (damage to the oesophagus causing burning sensation, chronic cough, shortness of breath, and difficulty swallowing, only with prolonged-release tablets), gastric mucosal inflammation (gastritis), anal and rectal pain (only with prolonged-release tablets), oral mucosal inflammation, tongue inflammation, abdominal distension (only with immediate-release tablets), constipation, dry mouth, belching, flatulence.
• Hepatic 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), aspartate aminotransferase (another liver enzyme), and gamma-glutamyltransferase (another liver enzyme, only with immediate-release tablets).
• Skin: bullous dermatitis (blistering rash, only with intravenous injection formulation), pruritus, urticaria (edematous, red, and intensely itchy skin lesions), maculopapular rash (skin lesion with a papule or wart on a discolored spot, only with granules for oral suspension).
• Musculoskeletal disorders: muscle spasms (only with granules for oral suspension), musculoskeletal rigidity (only with intravenous injection formulation), muscle pain (only with prolonged-release tablets).
• Renal disorders: increased serum creatinine and serum urea (both effects, indicating impaired kidney function, only with intravenous injection formulation).
• General disorders: malaise (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 intravenous injection formulation), increased serum alkaline phosphatase and increased blood lactate dehydrogenase (the last two only with immediate-release tablets).

With frequency not known (frequency cannot be estimated from available data), the following have been observed:

• Infections: pseudomembranous colitis (diarrhoea that may become severe), erysipelas (skin redness of variable extent that may cause pain, itching, and fever).

• Blood disorders: decreased neutrophil count (a type of white blood cell), decreased platelets.

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

• Psychiatric disorders: psychotic disorder, confusion, depersonalization, depression, disorientation, hallucinations, hypnagogic hallucinations (attenuated perception of external stimuli).

• Nervous system: seizures, decreased or loss of taste sensation, olfactory disturbance, loss or decreased sense of smell, tingling, numbness, or burning sensations in hands, feet, arms, or legs.

• Ear: deafness.

• Cardiac disorders: torsades de pointes (a type of ventricular tachycardia), ventricular tachycardia (accelerated heartbeat exceeding 100 beats per minute with at least 3 consecutive irregular beats).

• Vascular disorders: haemorrhage.

• Gastrointestinal disorders: acute pancreatitis (acute inflammation of the pancreas), tongue discoloration, tooth discoloration.

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

• Skin: Stevens-Johnson syndrome (widespread rash with blisters and skin peeling, mainly affecting genital, oral, and trunk areas), acute generalized exanthematous pustulosis (widespread scaly red rash with subcutaneous bumps and blisters, accompanied by fever, primarily located in skin folds, trunk, and upper limbs), and toxic epidermal necrolysis (widespread blistering and skin peeling, particularly around mouth, nose, eyes, and genitals, causing widespread skin shedding (more than 30% of body surface area), flu-like symptoms with skin rash, fever, lymph node swelling, 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 any of these reactions occur, treatment with clarithromycin should be stopped immediately and you should consult your doctor for appropriate management.

• Musculoskeletal disorders: rhabdomyolysis (muscle breakdown that may cause kidney damage), myopathy (muscle disease of various causes).

• Renal disorders: kidney function failure, interstitial nephritis (inflammation of renal tubules).

• Laboratory tests: increased international normalized ratio (calculation to detect blood coagulation), prolonged prothrombin time (indicating blood coagulation deficiency), and abnormal urine color.

Specific adverse effects

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

Post-marketing reports have indicated central nervous system effects (e.g., somnolence and confusion) with concomitant use of clarithromycin and triazolam. Patient monitoring is advised.

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

Rarely, there have been reports of prolonged-release clarithromycin tablets appearing in faeces. Many of these cases occurred in patients with gastrointestinal anatomical disorders [including ileostomy or colostomy (surgery to divert intestinal waste artificially from the ileum or colon)] or functional disorders (conditions caused by a bodily defect) with shortened gastrointestinal transit time. In several reports, tablet residues appeared in the context of diarrhoea. Patients who notice tablet residues in their faeces and do not experience improvement should switch to another formulation of clarithromycin (e.g., suspension) or to another antibiotic.

Adverse effects in children and adolescents:

Clinical trials with paediatric clarithromycin suspension have been conducted in children aged 6 months to 12 years. Therefore, children under 12 years of age should take paediatric clarithromycin suspension. There are insufficient data to recommend a dosing regimen for intravenous clarithromycin formulation in patients under 18 years of age.

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 other immunocompromised patients treated with high doses of clarithromycin over long periods for mycobacterial infections, it is often difficult to distinguish adverse effects possibly associated with clarithromycin administration from those caused by the underlying disease or other conditions associated 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 were: nausea, vomiting, taste disturbance, abdominal pain, diarrhoea, skin rash, flatulence, headache, constipation, hearing disturbances, and elevated transaminases (which may indicate liver, pancreas, heart, or muscle involvement). Less frequently observed were breathing difficulty, insomnia, and dry mouth. Incidence rates were similar in patients receiving 1,000 mg and 2,000 mg, but were generally 3 to 4 times higher in those receiving a total daily dose of 4,000 mg of clarithromycin.

In these immunocompromised patients, approximately 2% to 3% receiving 1,000 mg or 2,000 mg of clarithromycin daily developed severely abnormal elevations in transaminase levels, as well as abnormally low white blood cell and platelet counts. A smaller percentage of patients in both dosage groups also had elevated blood urea nitrogen levels (which may indicate reduced kidney function). In patients receiving 4,000 mg daily, slightly higher incidences of abnormal values were observed for all parameters except white blood cell count.

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

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of KLACID 500 mg lyophilisate for solution for infusion

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

No special storage conditions are required.

• • Reconstituted solution (500 mg in 10 ml of water for injections): may be stored for 24 hours at 25°C and for 48 hours at 2°C–8°C.
• The final reconstituted solution (reconstituted solution for infusion added to 250 ml of diluent, respectively for each diluent mentioned) may 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 lyophilisate after the expiry date stated on the container after EXP. The expiry date refers to the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. If you have any doubts, ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Klacid 500 mg lyophilisate for solution for infusion

The active substance in Klacid 500 mg lyophilisate is clarithromycin. Each vial contains 739.5 mg of clarithromycin lactobionate, equivalent to 500 mg of clarithromycin.

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

Appearance of the product and contents of the container

White or almost white lyophilised powder in the form of a cake with a slight aromatic odour, in a glass vial. Each pack contains 1 vial of 15 ml.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Viatris Healthcare Limited
Damastown Industrial Park
Mulhuddart, Dublin 15
Dublin
Ireland

Manufacturer:

Delpharm Saint Remy
Rue de l'Isle
28380 Saint-Remy-sur-Avre
France

Further information on this medicinal product is available from the local representative of the Marketing Authorisation Holder:

Viatris Pharmaceuticals, S.L.
C/ General Aranaz, 86
28027 - Madrid
Spain

Date of the most recent review of this summary: March 2024

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

INFORMATION FOR HEALTHCARE PROFESSIONALS:

Adults:

The recommended dose in adults and adolescents (12 to 18 years of age) is 1 g per day, divided into two equal doses, each administered by intravenous infusion after further dilution with an appropriate intravenous diluent, over a period of 60 minutes. Currently, there are no data to justify the intravenous use of clarithromycin in children. Clarithromycin must not be administered as a bolus injection or intramuscularly.

Elderly patients:

Same dose as for adults.

Dosing in patients with mycobacterial infections:

Although there are currently no data on the use of intravenous clarithromycin in immunocompromised patients, data are available on the use of oral clarithromycin in HIV-infected patients. For 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.

Intravenous treatment may be administered for 2–5 days in severely ill patients and should be switched to oral clarithromycin treatment whenever possible, as determined by the physician.

Renal impairment:

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

Hepatic impairment:

Clarithromycin must not be administered to patients with severe hepatic impairment combined with renal impairment. (see section 4.3)

Paediatric population:

There are insufficient data to recommend a dosing regimen for intravenous clarithromycin in patients under 18 years of age.

Instructions for preparation/handling

1. Prepare the initial clarithromycin solution (reconstituted solution) by adding 10 ml of sterile water for injections to the 500 mg vial. Gently rotate until complete dissolution is achieved, with no visible residue of undissolved macroparticles (this may take up to 5 minutes). Only sterile water for injections should be used, as other diluents may cause precipitation during reconstitution. Do not use diluents containing preservatives or inorganic salts.

Note: When the product is reconstituted as described above, each ml of 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; if stored at 2°C–8°C, it should be used within 48 hours.

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

• 0.9% Sodium chloride
• 5% Glucose
• 5% Glucose in 0.3% Sodium chloride
• 5% Glucose in 0.45% Sodium chloride
• 5% Glucose in Ringer's Lactate solution
• Ringer's Lactate solution

The final diluted solution (the reconstituted solution added to 250 ml of the diluents listed above) may be stored for 6 hours at room temperature (25°C) or for 48 hours under refrigeration (2°C–8°C).

Other medicinal products or chemical agents must not be added to the final mixture unless compatibility with respect to physical or chemical stability has been demonstrated.

Pharmaceutical incompatibilities

Not described.

Overdose

In case of overdose, treatment should be discontinued and appropriate supportive measures initiated.

Adverse reactions accompanying overdose should be managed by rapid elimination of unabsorbed drug and supportive measures.

Clarithromycin levels are not expected to be substantially affected by hemodialysis or peritoneal dialysis.