Klacid

Leaflet attached to the packaging: patient information

Klacid, 500 mg, powder for concentrate for solution for infusion

Clarithromycin

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Klacid and what is it used for
• 2. Important information before taking Klacid
• 3. How to take Klacid
• 4. Possible side effects
• 5. How to store Klacid
• 6. Contents of the packaging and other information

1. What is Klacid and what is it used for

Klacid contains the active substance clarithromycin. It is a macrolide antibiotic that inhibits the growth of bacteria that cause infections.
Klacid in the form of powder for concentrate for solution for infusion is indicated for use in adults and children over 12 years of age for the treatment of infections caused by microorganisms susceptible to clarithromycin, when intravenous administration of an antibiotic is necessary. These infections include:

• upper respiratory tract infections
• lower respiratory tract infections
• skin and soft tissue infections
• disseminated or localized infections caused by mycobacteria

2. Important information before taking Klacid

When not to take Klacid

• If the patient is allergic to clarithromycin or other macrolide antibiotics (such as azithromycin, erythromycin) or any of the other ingredients of this medicine (listed in section 6).
• If the patient is taking ergot alkaloids, such as ergotamine or dihydroergotamine (used in migraine), or midazolam orally (used in anxiety and insomnia).
• If the patient is taking medicines that may cause severe heart rhythm disturbances.
• If the patient is taking astemizole or terfenadine (used in allergies), cisapride or domperidone (used in gastrointestinal disorders), pimozide (used in psychiatric disorders), as concomitant use with Klacid may cause severe heart rhythm disturbances.
• If the patient is taking ticagrelor, ivabradine, or ranolazine (used in the treatment of angina pectoris or to reduce the risk of myocardial infarction or stroke).
• If the patient has low potassium or magnesium levels in the blood (hypokalemia or hypomagnesemia).
• If the patient is taking lovastatin or simvastatin (statins used to lower blood cholesterol levels).
• If the patient has severe liver failure with concomitant renal failure.
• If the patient or their family members have a history of heart rhythm disturbances (ventricular arrhythmias, including torsades de pointes) or electrocardiogram (ECG) abnormalities known as "long QT syndrome".
• If the patient is taking colchicine (used in the treatment of gout).
• If the patient is taking a medicine containing lomitapide.

Warnings and precautions

If the patient has any of the following conditions, they should discuss this with their doctor before starting treatment with Klacid.

• The patient is pregnant or thinks they may be pregnant.
• The patient has kidney or liver function disorders.
• The patient has coronary artery disease, severe heart failure, or bradycardia.
• The patient is taking any of the medicines listed in the "Klacid and other medicines" section.

If any of the following situations occur during treatment with Klacid, the patient should tell their doctor.

• Severe hypersensitivity reactions, such as rash, urticaria, angioedema, or anaphylaxis. The patient should immediatelyconsult a doctor, who will provide appropriate treatment.
• Diarrhea, especially acute or prolonged. The patient should tell their doctor as soon as possible. If necessary, the doctor will prescribe appropriate treatment. The patient should not take anti-diarrheal medicines.
• Symptoms of liver function disorders, such as loss of appetite, jaundice, dark urine, itching, or abdominal pain. The patient should stop treatment and consult a doctor.
• New infections (superinfections) with bacteria resistant to clarithromycin or fungi, especially during prolonged use of the antibiotic. The doctor will prescribe appropriate treatment.

In addition, during treatment with Klacid, the following may occur:

• Cross-resistance of bacteria (bacteria resistant to clarithromycin may also be resistant to other macrolide antibiotics and lincosamides and clindamycin)

If symptoms of hearing organ or vestibular damage occur (see section 4), it is recommended to perform appropriate control tests after completing treatment.

Klacid and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.

The patient must inform their doctor if they are taking any of the following medicines, as their use with Klacid is contraindicated:

• Ergot alkaloids, such as ergotamine or dihydroergotamine (used in migraine)
• Astemizole or terfenadine (used in allergies)
• Cisapride or domperidone (used in gastrointestinal disorders)
• Pimozide (used in psychiatric disorders)
• Ticagrelor, ranolazine (used in heart and circulation diseases)
• Colchicine (used in gout)
• Statins - lovastatin, simvastatin (used to lower blood cholesterol levels)
• Oral midazolam (used in anxiety or insomnia)

The patient should inform their doctor if they are taking any of the following medicines, as special caution is required when using them with Klacid:

Klacid:

• Rifampicin, rifapentine, rifabutin (antibiotics used in the treatment of tuberculosis)
• Fluconazole, itraconazole (antifungal medicines)
• Atazanavir, efavirenz, etravirine, nevirapine, ritonavir, saquinavir, zidovudine (used in the treatment of HIV infection)
• Digoxin, quinidine, disopyramide, verapamil, amlodipine, diltiazem (used in the treatment of heart rhythm disorders or hypertension)
• Alprazolam, triazolam, midazolam administered intravenously or orally, or into the mouth (used in anxiety or insomnia)
• Warfarin or other anticoagulant medicines, such as dabigatran, rivaroxaban, apixaban, edoxaban (used to thin the blood)
• Quetiapine or other atypical antipsychotic medicines
• Carbamazepine, valproate, phenytoin (antiepileptic medicines)
• Methylprednisolone (anti-inflammatory medicine)
• Omeprazole (medicine that reduces stomach acid production)
• Cilostazol (used in intermittent claudication, which is characterized by leg pain during exercise and relieved by rest)
• Cyclosporine, tacrolimus, sirolimus (used in organ transplantation)
• Sildenafil, tadalafil, vardenafil (used in erectile dysfunction)
• Ibrutinib or vinblastine (used in chemotherapy for cancer)
• Theophylline (used in asthma)
• Tolterodine (used in urinary incontinence)
• Phenobarbital (antiepileptic medicine)
• St. John's wort (herbal medicine used in mild depression)
• Sulfonylurea, nateglinide, repaglinide, insulin (used in diabetes)

This is also important for the following medicines:

• Hydroxychloroquine or chloroquine (used in the treatment of rheumatoid arthritis, or to prevent or treat malaria). Taking these medicines with clarithromycin may increase the risk of heart rhythm disturbances and other serious side effects affecting the heart.
• Oral, injectable, or inhaled corticosteroids (used to suppress the immune system, which is useful in the treatment of many different diseases)

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before taking this medicine.
The safety of clarithromycin in pregnancy and breastfeeding has not been established.
Klacid may be used in pregnancy only if the doctor believes that the benefits to the mother outweigh the potential risks to the fetus.
Since clarithromycin passes into breast milk, breastfeeding women should exercise caution when taking Klacid.

Driving and using machines

The medicine may cause dizziness, confusion, and disorientation, which may affect the ability to drive and use machines.
The medicine contains less than 1 mmol (23 mg) of sodium per dose, which means it is essentially "sodium-free".

3. How to take Klacid

This medicine should always be taken as directed by the doctor. If the patient has any doubts, they should consult their doctor or pharmacist.
The medicine is administered intravenously.
Adults
The recommended daily dose of clarithromycin for infusion is 1 gram, given in two divided doses of 500 mg each.
The powder in the vial is dissolved and then diluted in an appropriate solvent (the method of preparing the infusion solution is described in the part of the leaflet intended for medical staff). The dose is administered intravenously over at least 60 minutes.
The medicine should not be administered as a single rapid injection (bolus) or intramuscularly.
Depending on the severity of the infection, intravenous administration of clarithromycin is limited to 2-5 days, and oral administration of the medicine should be started as soon as possible.
Children and adolescents
There are no adequately documented data on the use and dosage of Klacid in the form of a solution for infusion in patients under 12 years of age.
In adolescents over 12 years of age, the dosage is the same as for adults.
Patients with renal impairment
Depending on the degree of renal impairment, the doctor may recommend reducing the dose of the medicine by half, i.e., to 500 mg per day.
Patients with impaired immune function infected with mycobacteria
There are no clinical data on the use of Klacid in the form of a solution for infusion in patients with impaired immune function, but there are data on the use of oral forms of clarithromycin in patients with HIV infection. In the treatment of disseminated or localized infections caused by mycobacteria, the recommended daily dose in adults is 500 mg of clarithromycin twice daily.

Using more than the recommended dose or missing a dose of Klacid

The medicine is administered to the patient by medical staff. If the patient suspects that they have been given a higher dose than recommended or have missed a dose, they should tell their doctor or nurse.

4. Possible side effects

Like all medicines, Klacid can cause side effects, although not everybody gets them.

If the patient experiences any of the following side effects at any stage of treatment, they should stop taking Klacid and consult their doctor immediately:

• Anaphylactic shock or anaphylactoid reaction - a life-threatening allergic reaction, characterized by confusion, pallor, low blood pressure, sweating, oliguria, tachypnea, weakness, and syncope
• Allergic reactions: rash (frequent), itching, urticaria (infrequent), angioedema of the face, tongue, lips, eyes, and throat, difficulty breathing
• Severe skin reactions:
• Acute generalized exanthematous pustulosis - a red, scaly rash with papules and blisters, and pustular psoriasis (infrequent)
• Stevens-Johnson syndrome - a severe skin and mucous membrane disorder, characterized by a sudden onset of fever and blisters, which resolve spontaneously after discontinuation of the medicine; a severe disease characterized by blisters and erosions on the skin, in the mouth, eyes, and genital areas, fever, and arthralgia
• Toxic epidermal necrolysis - a severe, rapidly progressing disease, characterized by large, flaccid blisters, extensive skin necrosis, and fever
• DRESS syndrome - a severe, life-threatening drug rash, characterized by an increase in eosinophils and involvement of internal organs
• Severe or prolonged diarrhea, which may be bloody or contain mucus. Diarrhea may occur even two months after completion of treatment with clarithromycin. In such cases, the patient should consult their doctor.
• Jaundice, skin discoloration, dark urine, itching, or abdominal pain. These may be symptoms of liver failure.
• Cardiac arrest, ventricular tachycardia, extrasystoles, palpitations, changes in the ECG (QT interval prolongation) (infrequent)
• Loss of consciousness (infrequent)
• Pulmonary embolism (infrequent; characterized by shortness of breath, chest pain, cough, cyanosis) These side effects occur with unknown frequency, unless otherwise specified.

Other side effects

In clinical trials and after marketing of clarithromycin in the form of powder for concentrate for solution for infusion, very common(more than 1 in 10 patients) reports of phlebitis at the injection site were noted.
In patients taking clarithromycin intravenously or orally, the following side effects were common(between 1 in 100 and 1 in 10 patients):

• Pain at the injection site, phlebitis at the injection site, inflammation at the injection site
• Insomnia
• Taste disturbances, headache, changes in taste perception
• Vasodilation
• Diarrhea, vomiting, nausea, abdominal pain
• Abnormal liver function test results

Side effects reported uncommonly(between 1 in 1000 and 1 in 100 patients):

• Conjunctivitis, candidiasis (fungal infection), vaginal infection
• Decreased white blood cell count
• Anorexia, decreased appetite
• Agitation
• Dyskinesia (involuntary, uncoordinated movements of the limbs or body), dizziness, somnolence, tremors
• Balance disorders, hearing disturbances, tinnitus
• Asthma
• Esophagitis, gastritis, stomatitis, glossitis, constipation, dry mouth, eructation, flatulence
• Increased liver enzyme activity: alanine aminotransferase, aspartate aminotransferase
• Musculoskeletal stiffness
• Increased creatinine and urea levels in the blood, abnormal albumin/globulin ratio
• Asthenia (weakness, lack of energy)

The following side effects have been reported with an unknown frequency(frequency cannot be estimated from available data) after marketing of different forms of Klacid (tablets, granules for oral suspension, powder for concentrate for solution for infusion):

• Rash
• Agranulocytosis (decreased granulocyte count), thrombocytopenia (decreased platelet count)
• Acne
• Psychotic disorder, confusion, depersonalization, depression, disorientation, hallucinations, unusual dreams, mania
• Seizures, ageusia, dysgeusia, anosmia, paresthesia (numbness, tingling)
• Deafness
• Heart rhythm disturbances, such as torsades de pointes, ventricular tachycardia, atrial fibrillation
• Hemorrhage
• Acute pancreatitis, tooth discoloration, tongue discoloration
• Myopathy (muscle disease with muscle weakness)
• Kidney failure, interstitial nephritis
• Changes in laboratory test results (increased INR, prolonged prothrombin time, abnormal urine color)

Patient with impaired immune function
In addition to symptoms related to the course of the disease, the following side effects have been observed in adult patients with impaired immune function:

• Nausea, vomiting, changes in taste perception, constipation, abdominal pain, diarrhea, flatulence, dry mouth
• Headache, hearing disturbances
• Rash
• Dyspnea, insomnia
• Abnormal laboratory test results: increased aspartate aminotransferase and alanine aminotransferase activity, increased urea levels in the blood, and decreased platelet and white blood cell counts.

Reporting side effects
If the patient experiences any side effects, including those not listed in this leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products,
Al. Jerozolimskie 181C, 02-222 Warsaw,
Phone: 22 49 21 301,
Fax: 22 49 21 309
website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Klacid

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "EXP". The expiry date refers to the last day of the month stated.
Batch number is stated on the packaging after "Lot".
Store at a temperature not exceeding 30°C.
Store in the original packaging.
The infusion solution should be stored at a temperature between 2°C and 8°C - use within 24 hours.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Klacid contains

• The active substance of the medicine is clarithromycin. One vial contains 500 mg of clarithromycin.
• The other ingredients are lactic acid and sodium hydroxide to adjust the pH.

What Klacid looks like and what the packaging contains

Klacid, powder for concentrate for solution for infusion, is a white or almost white powder.
The packaging is a 15 ml Type I Ph.Eur. glass vial, sealed with a gray halobutyl silicone lyophilized stopper W4416/50 (Igloo).

Marketing authorization holder

Viatris Healthcare Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw

Manufacturer

Delpharm Saint Remy
Rue de l’Isle
28380 Saint-Rémy-sur-Avre
France
To obtain more detailed information about this medicine, the patient should contact the marketing authorization holder:
Viatris Healthcare Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw
Phone: 22 546 64 00

Date of last revision of the leaflet: -------------------------------[perforated line separating the patient information leaflet]------------------------

The following information is intended for medical staff only

INSTRUCTIONS FOR THE PERSON ADMINISTERING THE MEDICINE

Klacid, 500 mg, powder for concentrate for solution for infusion
Clarithromycin
The powder in the vial should be dissolved and then diluted in an appropriate solvent (see below: Method of preparing the infusion solution). The dose should be administered intravenously over at least 60 minutes.
The medicine should not be administered as a single rapid injection (bolus) or intramuscularly.

METHOD OF PREPARING THE INFUSION SOLUTION

• A. Preparation of the basic solution

10 ml of water for injection should be injected into the vial with the medicine. Shake until the contents of the vial are dissolved. Only water for injection should be used for dissolution. Other solvents may cause precipitation.
1 ml of the basic solution, prepared as described above, contains 50 mg of clarithromycin.
The basic solution shows chemical and physical stability for 48 hours at 5°C or for 24 hours at 25°C. From a microbiological point of view, the product should be used immediately after preparation. The user is responsible for not using the product immediately after preparation or not following the storage time and conditions. As a rule, the solution should not be stored for more than 24 hours at 2°C to 8°C. The exception is when the solution has been prepared in controlled and validated aseptic conditions.

• B. Preparation of the infusion solution

The basic solution (500 mg in 10 ml of water for injection) should be added to 250 ml of one of the following solutions: 5% glucose solution in Ringer's solution with lactate, 5% glucose solution, Ringer's solution with lactate, 5% glucose solution in 0.3% sodium chloride solution, Normosol-M in 5% glucose solution, Normosol-R in 5% glucose solution, 5% glucose solution in 0.45% sodium chloride solution, 0.9% sodium chloride solution.
The infusion solution shows chemical and physical stability for 48 hours at 5°C or for 6 hours at 25°C. From a microbiological point of view, the infusion solution should be used immediately after preparation. The user is responsible for not using the product immediately after preparation or not following the storage time and conditions. As a rule, the solution should not be stored for more than 24 hours at 2°C to 8°C. The exception is when the solution has been prepared in controlled and validated aseptic conditions.
Note.There are no clinical data on the compatibility of Klacid with other solutions for intravenous administration.