Taclar

Package leaflet: Information for the patient

Taclar, 500 mg, powder for solution for infusion
Clarithromycinum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What Taclar is and what it is used for
2. Important information before using Taclar
3. How to use Taclar
4. Possible side effects
5. How to store Taclar
6. Contents of the pack and other information

1. What Taclar is and what it is used for

Taclar contains the active substance – clarithromycin. It is a macrolide antibiotic which
inhibits the growth of bacteria causing infections.
Taclar as a powder for solution for infusion is indicated for use in adults and children aged 12 years and older
for the treatment of infections caused by microorganisms sensitive to clarithromycin, when intravenous
administration of the 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 using Taclar

When not to use Taclar

• 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 any of the following medicines:
• medicines that may cause severe heart rhythm disorders, including:
• astemizole or terfenadine (medicines used in allergies)
• cisapride (a medicine used for gastrointestinal motility disorders)
• pimozide (a medicine used for psychiatric disorders)
• ergot alkaloids such as ergotamine or dihydroergotamine (medicines used, among others, in migraine)
• lovastatin, simvastatin (statin medicines used to reduce blood cholesterol levels)
• midazolam administered orally (a medicine used in anxiety states and insomnia)
• colchicine (a medicine used in the treatment of gout)
• a medicine containing lomitapide (a medicine used in patients with high cholesterol to reduce it)
• If the patient is taking medicines called ticagrelor, ivabradine or ranolazine (used in the treatment of angina pectoris or to reduce the risk of heart attack or stroke).
• If the patient has low blood potassium or magnesium levels (hypokalaemia or hypomagnesaemia).
• If the patient has previously experienced heart rhythm disorders (ventricular arrhythmias, including torsade de pointes) either personally or in family members, or has abnormalities on electrocardiogram (ECG, recording of the heart's electrical activity) known as "long QT syndrome".
• If the patient has severe hepatic impairment associated with renal impairment.

Warnings and precautions
If any of the following situations apply to the patient, discuss them with the doctor before starting
treatment with Taclar.

• The patient is pregnant or suspects she may be pregnant.
• The patient has impaired kidney or liver function.
• The patient has been diagnosed with coronary artery disease, severe heart failure, or bradycardia (slow heart rate).
• The patient is taking any of the medicines listed in the section "Taclar with other medicines".

If any of the following situations occur during treatment with Taclar, inform the doctor immediately.

• Severe hypersensitivity reactions such as maculopapular rash, urticaria, petechiae, laryngeal oedema, bronchospasm. Immediate medical attention is required, and appropriate treatment will be initiated.
• Diarrhoea, especially if acute or prolonged. Inform the doctor as soon as possible. If necessary, the doctor will recommend appropriate treatment. Do not use antidiarrhoeal medicines.
• Symptoms suggesting liver dysfunction such as loss of appetite, jaundice, dark urine, pruritus, or abdominal pain. Discontinue treatment and consult a doctor immediately.
• New infection (superinfection) with bacteria resistant to clarithromycin or fungi, especially during prolonged antibiotic use. The doctor will recommend appropriate treatment.

Additionally, during treatment with Taclar, the following may occur:

• Bacterial cross-resistance (bacteria resistant to clarithromycin may also show resistance to other macrolide antibiotics as well as to lincomycin and clindamycin).

Taclar with other medicines
Tell your doctor about all medicines the patient is currently taking or has recently taken,
as well as any medicines the patient plans to take.
It is essential to inform the doctor if the patient is taking any of the following medicines,
because their use together with Taclar is contraindicated:

• astemizole or terfenadine (medicines used in allergies)
• cisapride (a medicine used for gastrointestinal motility disorders)
• pimozide (a medicine used for psychiatric disorders)
• ergot alkaloids such as ergotamine or dihydroergotamine (medicines used, among others, in migraine)
• statins - lovastatin, simvastatin (medicines that lower blood cholesterol levels)
• midazolam administered orally (a medicine used in anxiety or insomnia)
• colchicine (a medicine used in gout)

Inform the doctor if the patient is taking any of the following medicines, because
special caution is necessary when using them together with Taclar:

• 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 mucosally (medicines used in anxiety or insomnia)
• warfarin or any other anticoagulant, e.g. dabigatran, rivaroxaban, apixaban, edoxaban (medicines used to thin the blood)
• quetiapine or other atypical antipsychotics
• carbamazepine, valproate, phenytoin (antiepileptic medicines)
• atorvastatin, rosuvastatin (statins - medicines that lower blood cholesterol levels)
• methylprednisolone (an anti-inflammatory medicine)
• omeprazole (a medicine that reduces gastric acid secretion)
• cilostazol (a medicine used in intermittent claudication, which causes leg muscle pain during exercise that resolves with short rest)
• cyclosporine, tacrolimus, sirolimus (medicines used, among others, after organ transplantation)
• sildenafil, tadalafil, vardenafil (medicines used in erectile dysfunction)
• vinblastine (a medicine used in cancer chemotherapy)
• theophylline (a medicine used in bronchial asthma)
• tolterodine (a medicine used in urinary incontinence)
• phenobarbital (an anticonvulsant medicine)
• St. John's wort (Hypericum perforatum) (a herbal medicine used in mild depression)
• sulfonylureas, nateglinide, repaglinide, insulin (medicines used in diabetes)

This is also important when using the following medicines:

• hydroxychloroquine or chloroquine (used in the treatment of, among others, rheumatoid arthritis, and in the treatment or prevention of malaria). Taking these medicines together with clarithromycin may increase the risk of heart rhythm disturbances and other serious adverse effects affecting the heart.
• corticosteroids administered orally, by injection, or by inhalation (used to suppress the immune system, which is useful in treating many different conditions).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become
pregnant, she should consult a doctor or pharmacist before using this medicine.
The safety of clarithromycin use during pregnancy and breastfeeding has not been established.
Taclar may be used during pregnancy only if, in the doctor's opinion, the benefit to the mother
outweighs the potential risk to the foetus.
Since clarithromycin passes into breast milk, women who are breastfeeding should exercise
particular caution when using Taclar.

Driving and operating machinery
The medicine may cause dizziness, confusion, and disorientation, which may affect the ability
to drive vehicles and operate machinery.

3. How to use Taclar

This medicine should always be used as directed by the physician. In case of doubt, consult
your doctor or pharmacist.
This is an intravenous preparation.
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 must be dissolved and then diluted in an appropriate solvent
(preparation method for the infusion solution is described in the section of the package leaflet intended for medical personnel). The dose should be administered intravenously over an infusion period of at least 60 minutes.
The medicine must not be administered as a single, rapid injection ( bolus ) or by intramuscular injection.
Depending on the severity of infection, intravenous clarithromycin infusion should be limited
to 2–5 days; oral administration of the drug should be initiated as soon as possible.
Children and adolescents
There is insufficient documented evidence regarding the use and dosing of Taclar infusion formulation
in patients under 12 years of age.
For adolescents aged 12–18 years, dosing is the same as for adults.
Patients with renal impairment
Depending on the degree of renal impairment, the physician may recommend reducing the dose by half,
i.e. to 500 mg per day.
Immunocompromised patients infected with mycobacteria
There are currently no clinical data available on the use of Taclar infusion formulation
in immunocompromised patients; however, data are available on the use of oral formulations of
clarithromycin in HIV-infected patients. For the treatment of disseminated or localized infections
caused by mycobacteria, the recommended daily dose in adults is 500 mg of clarithromycin
twice daily.
Use of a higher than recommended dose or omission of a dose of Taclar
The medicine is administered to the patient by medical personnel. If the patient suspects that
an overdose has been administered or a dose has been missed, they should inform the doctor or
nurse immediately.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the following adverse reactions occur in a patient, at any stage of treatment with the medicine,
stop taking Taclar immediately and consult a doctor without delay:

• Severe or prolonged diarrhoea, possibly with blood or mucus in the stool (pseudomembranous colitis). Diarrhoea may occur even up to two months after completing treatment with clarithromycin. In such a case, medical advice should also be sought.
• Allergic reactions:
• Rash, difficulty breathing, fainting, or swelling of the face, tongue, lips, eyes, or throat (anaphylactoid reaction, hypersensitivity)
• Anaphylactic reaction (acute, life-threatening allergic reaction involving, among others, disturbances of the circulatory and respiratory systems), angioedema
• Severe skin reactions:
• Painful peeling of the skin, mouth, lips, eyes, and genitals (symptoms of an allergic reaction known as Stevens-Johnson syndrome or toxic epidermal necrolysis [Lyell's syndrome])
• Red, scaly rash with subcutaneous nodules and blisters (symptoms of acute generalized exanthematous pustulosis [AGEP])
• Rare skin allergic reaction causing a serious illness characterized by oral and lip ulcers, skin rash, fever, and internal organ inflammation (DRESS syndrome)
• Yellowing of the skin (jaundice), skin irritation, pale-coloured stools, dark-coloured urine, abdominal tenderness, or loss of appetite. These may be symptoms of liver inflammation or liver failure.
• Muscle pain or muscle weakness known as rhabdomyolysis (a syndrome caused by breakdown of muscle tissue, potentially leading to kidney damage).

In clinical trials and post-marketing surveillance of clarithromycin as a powder for solution for infusion,
very common (reported in more than 1 in 10 patients) adverse reactions included
phlebitis at the injection site.

In patients receiving clarithromycin intravenously or orally, the following adverse reactions were reported commonly (occur in 1 to 10 out of 100 patients):

• Pain at injection site, inflammation at injection site
• Insomnia
• Taste disturbances, headache, altered sense of taste
• Vasodilation
• Diarrhoea, vomiting, dyspepsia, nausea, abdominal pain
• Abnormal liver function test results
• Rash, excessive sweating

Adverse reactions reported uncommonly (occur in 1 to 10 out of 1,000 patients):

• Connective tissue inflammation, candidiasis (fungal infection), vaginal infection
• Decreased white blood cell count, increased platelet count
• Anorexia, decreased appetite
• Anxiety
• Loss of consciousness, dyskinesia (involuntary, uncoordinated movements of limbs or whole body), dizziness, somnolence, tremor
• Balance disorders, hearing loss, tinnitus
• Cardiac arrest, atrial fibrillation, extrasystoles, palpitations, ECG changes (prolongation of QT interval)
• Asthma, pulmonary embolism, epistaxis
• Oesophagitis, gastritis, stomatitis, glossitis, abdominal distension, constipation, dry mouth, belching, flatulence
• Increased liver enzyme activity
• Bullous dermatitis, pruritus, urticaria
• Musculoskeletal stiffness
• Increased blood creatinine, increased blood urea, abnormal albumin/globulin ratio
• Asthenia (weakness, lack of energy), malaise, fever, chest pain, chills

The following adverse reactions have been reported with unknown frequency (frequency cannot be estimated from available data) following the marketing of various formulations of the medicine containing the active substance clarithromycin (tablets, granules for oral suspension, powder for concentrate solution for infusion):

• Pseudomembranous colitis
• Erythema
• Agranulocytosis (decreased granulocyte count), thrombocytopenia (decreased platelet count)
• Acne
• Psychotic disorder, confusion, depersonalization, depression, disorientation, hallucinations, unusual dreams, mania
• Seizures, ageusia (loss of taste), parosmia (distorted sense of smell), anosmia (loss of smell), paresthesia (numbness, tingling)
• Deafness
• Cardiac arrhythmias, ventricular tachycardia, ventricular fibrillation
• Bleeding and changes in coagulation parameters (especially if the patient is concurrently taking oral anticoagulants)
• Acute pancreatitis, tongue discoloration, tooth discoloration
• Liver failure, hepatocellular jaundice
• Muscle diseases (myopathies) presenting as muscle weakness, in some cases difficulty in muscle relaxation, muscle atrophy
• Renal failure, interstitial nephritis
• Changes in diagnostic test results (increased international normalized ratio [INR], prolonged prothrombin time, abnormal urine colour)

Patients with reduced immunity
In addition to symptoms related to the underlying disease, the following adverse reactions have been observed in adult patients with impaired immunity:

• Nausea, vomiting, taste disturbances, constipation, abdominal pain, diarrhoea, flatulence, dry mouth
• Headache, hearing disturbances
• Rash
• Dyspnoea, insomnia
• Abnormal laboratory test results: increased aspartate aminotransferase (AspAT) and alanine aminotransferase (AlAT) activity, increased blood urea nitrogen, decreased platelet and white blood cell counts.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: 22 49 21 301
Fax: 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Taclar

Keep the medicine out of the sight and reach of children.
Store below 25°C. Protect from light.
Do not use this medicine after the expiry date (EXP) stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

The active substance of the medicine is clarithromycin in the form of clarithromycin lactobionate.
One vial contains 500 mg of clarithromycin.
The medicine does not contain any other ingredients.
What Taclar looks like and contents of the pack
White or almost white lyophilisate in the form of a disc or fragments of various sizes; after dissolution
in water for injections, a colourless, clear solution is obtained.
Packaging: 1 vial or 10 vials in a cardboard box.
Marketing Authorisation Holder and Manufacturer
Tarchomin Pharmaceutical Works "Polfa" Joint Stock Company
A. Fleminga 2 Street
03-176 Warsaw
Telephone number: 22-811-18-14
For more detailed information about this medicine, please contact the representative of the marketing authorisation holder.

Information intended exclusively for healthcare professionals

• Administration method

Clarithromycin as a solution at a concentration of 2 mg/ml should be administered by intravenous infusion over a period of at least 60 minutes.
It must not be administered as a single rapid injection (bolus) or by intramuscular injection.

• Instructions for preparation of solutions

Stock solution for infusion preparation
Inject 10 ml of water for injections into the vial containing 500 mg of clarithromycin. Shake until the contents of the vial are completely dissolved.
1 ml of this prepared stock solution contains 50 mg of clarithromycin.
Store the solution at 2°C to 8°C and use within 24 hours.

Infusion solution
Dilute the stock solution (500 mg in 10 ml of water for injections) to 250 ml with 5% glucose solution or 0.9% sodium chloride solution.
1 ml of the resulting intravenous infusion solution contains 2 mg of clarithromycin.
Store the solution at 2°C to 8°C and use within 24 hours.
Intravenous infusion solutions prepared in 5% glucose solution or 0.9% sodium chloride solution remain stable for 6 hours at 25°C.
Any unused portions of the medicinal product or waste materials should be disposed of in accordance with local regulations.

• Pharmaceutical incompatibilities

None reported.
The medicinal product Taclar, powder for solution for infusion, should be dissolved and then diluted only in solvents recommended by the manufacturer.
There are currently no clinically documented studies on pharmaceutical compatibility with other infusion solutions.
No drugs or chemical substances should be added to the clarithromycin solution unless their influence on the physicochemical properties of the infusion solution has been previously tested.