Azylung

Patient Information Leaflet

Azylung 500 mg powder for concentrate for solution for infusion

Azithromycin (as dihydrate)
Generic medicine
Please read all of this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What Azylung is and what it is used for
2. What you need to know before taking Azylung
3. How to take Azylung
4. Possible side effects
5. How to store Azylung
6. Contents of the pack and other information

1. What Azylung is and what it is used for

Azylung belongs to a group of antibiotics called macrolides. It is used to treat localized infections
caused by bacteria in various parts of the body.
Which diseases are treated with Azylung?
Azylung is indicated for the treatment of severe infections or when oral treatments cannot be
used. Azylung is used to treat pneumonia (lung infection) or pelvic infections
(infections of the reproductive organs) caused by susceptible organisms.

2. What you need to know before taking Azylung

Do not take Azylung:

• if you are allergic to azithromycin, erythromycin, or to any other macrolide or ketolide antibiotic, or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Azylung:

• if you have an allergic reaction such as red or white spots on the skin, itching or skin irritation, swelling of the skin, larynx (throat), or tongue, or difficulty breathing. In such cases, you must stop treatment with Azylung
• if you have or have had kidney problems
• if you have or have had liver problems: your doctor may consider it necessary to monitor liver function or discontinue treatment
• if you have or have had an irregular heartbeat, particularly conditions such as long QT syndrome (detected by electrocardiogram or ECG equipment)
• if you experience palpitations or irregular heartbeat, dizziness, or feel faint while taking Azylung—in such cases, inform your doctor immediately
• if you are also receiving treatment with:
  • medicines used to treat heart rhythm disorders such as class IA and III antiarrhythmics (e.g. amiodarone, quinidine, sotalol, disopyramide, dofetilide, or procainamide)
  • cisapride (used to treat heartburn and gastrointestinal disorders)
  • terfenadine (used to treat allergies)
  • medicines used to treat mental health disorders (e.g. pimozide)
  • medicines used to treat depression (e.g. citalopram)
  • antibiotics belonging to the fluoroquinolone group (e.g. moxifloxacin and levofloxacin)
• if you develop diarrhoea or loose stools during or after treatment. In some cases, there is a risk of developing a severe intestinal inflammation known as pseudomembranous colitis. Do not take any medicine for diarrhoea without first consulting your doctor.

Other important precautions:

• You may develop fungal infections while taking azithromycin
• Severe allergic reactions may occur rarely
• Medicines known as ergot derivatives, such as ergotamine or dihydroergotamine (used for migraine or to reduce blood flow), must not be taken together with azithromycin
• You should also be cautious if you suffer from psychiatric or neurological disorders
• This medicine must not be used to treat infected burns
• Worsening of symptoms has been observed in patients with myasthenia gravis who were taking azithromycin.

Other medicines and Azylung
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicine.
Medicines can interact with each other or with other substances, causing unexpected reactions or, in some cases, increasing or reducing the expected effect. Therefore, you must inform your doctor about all medicines you are taking or have taken, especially:

• ergot derivatives such as ergotamine (used to treat migraine)
• digoxin (used to treat heart failure)
• warfarin or similar medicines used to prevent blood clotting
• cyclosporine (used to suppress the immune system and prevent or treat organ or bone marrow transplant rejection)
• cisapride (used to treat stomach problems)
• terfenadina (used to treat hay fever or skin allergies)
• nelfinavir (used to treat HIV infection (AIDS))
• zidovudine (for HIV). Azithromycin may reduce zidovudine levels in the blood; therefore, it should be taken at least 1–2 hours before or after zidovudine
• atorvastatin or other statins (medicines used to lower cholesterol levels)
• rifabutin (for HIV or tuberculosis)
• quinidine (used to treat heart rhythm problems) or other medicines used for irregular heartbeat (called antiarrhythmics)
• theophylline (used for respiratory problems).

Do not use Azylung with antacids (used to treat indigestion).
Pregnancy, breastfeeding, and fertility
Talk to your doctor or pharmacist before taking any medicine.
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Driving and using machines
Undesirable effects may occur that could affect your ability to drive or operate machinery (see section 4). It is advisable not to drive or operate machinery while taking azithromycin.
Azylung contains sodium
This medicine contains 101.5 mg of sodium per vial. This should be taken into consideration in patients on a low-sodium diet.

3. How to take Azylung

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts,
consult your doctor or pharmacist.
Your doctor will determine the appropriate dose and duration of treatment for you.
The following table describes the doses most commonly used in adults for the treatment of pneumonia
(lung infection) and pelvic infections.

Method and route of administration
Azylung must be administered by intravenous infusion.
This medicinal product must be reconstituted and diluted according to the instructions and administered as an intravenous infusion lasting no less than 60 minutes.

Duration of treatment
The duration of treatment will depend on the severity of your infection. Your doctor will provide you with specific guidance in this regard.

Particular patient groups
The use of Azylung is not recommended in children and growing adolescents.

Patients with kidney or liver problems:

• You must inform your doctor if you have kidney or liver problems, as the doctor may consider it necessary to adjust the prescribed dose.

For elderly patients, the same dose as in adults should be used.
If you have any doubts about the use of this medicinal product, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.

The following side effects have been reported:

Very common (affects more than 1 in 10 people)
Common (affects 1 to 10 in 100 people)
Uncommon (affects 1 to 10 in 1,000 people)
Rare (affects 1 to 10 in 10,000 people)
Very rare (affects less than 1 in 10,000 people)
Not known (frequency cannot be estimated from the available data)

Contact your doctor immediately if you experience any of the following symptoms – you may need urgent
medical treatment:

Uncommon:

• Allergic reactions, which may include: itching or skin rash, swelling of the face, lips, tongue and body, or difficulty breathing. The frequency of severe acute allergic reactions (anaphylactic reactions) is not known.

Rare:

• Yellowing of the skin and whites of the eyes (cholestatic jaundice)
• Red, scaly rash with pustules and blisters (exanthematous pustulosis)

Not known:

• Inflammation of the large intestine (colon) with diarrhoea (sometimes containing blood), abdominal pain and fever
• Serious liver disease or liver failure, which may include: sudden onset of fatigue associated with yellowing of the skin or whites of the eyes (jaundice), dark urine, tendency to bleed
• Severe skin reaction called Stevens-Johnson Syndrome. Signs may include: red or purple rash spreading within hours or days, blistering of the skin and mucous membranes, especially in the mouth, nose and eyes, skin peeling
• Severe skin reactions with swelling of the skin and mucous membranes and skin peeling over large areas of the body (erythema multiforme and toxic epidermal necrolysis)
• Kidney inflammation or kidney failure, which may include: increased need to urinate at night, muscle spasms and cramps, loss of appetite, feeling or being sick, unpleasant taste in the mouth

Other side effects:
Very common

• Diarrhoea

Common

• Headache
• Vomiting, abdominal pain, feeling unwell (nausea)
• Blood test abnormalities (decreased lymphocyte count, increased eosinophil count, increased basophils, increased monocytes, increased neutrophils), increased blood bicarbonate levels

Uncommon

• Fungal infection (candidiasis), vaginal infection, pneumonia, bacterial infections, throat infection, inflammation of the stomach and intestine, breathing problems, rhinitis, oral thrush (oral candidiasis)
• Decreased white blood cell count (neutropenia and leucopenia), increased count of certain types of white blood cells (eosinophilia)
• Loss of appetite (anorexia)
• Nervousness, insomnia
• Dizziness, drowsiness, altered taste, abnormal skin sensations such as tingling and numbness of limbs (paraesthesia)
• Visual disturbances
• Hearing disorders, sensation of spinning or dizziness (vertigo)
• Pounding or rapid heartbeat (palpitations)
• Flushing of the face, neck and upper chest (hot flushes)
• Shortness of breath, nosebleeds
• Constipation, flatulence, indigestion (dyspepsia), inflammation of the stomach lining (gastritis), difficulty swallowing, bloating (abdominal distension), dry mouth, belching, mouth ulcers, increased saliva production
• Inflammation of the liver (hepatitis)
• Itching, skin rash, hives, skin inflammation, dry skin, excessive sweating
• Joint disease (osteoarthritis), muscle pain, back pain, neck pain
• Pain when urinating, kidney pain
• Irregular uterine bleeding, testicular problems
• Fluid accumulation in tissues (oedema), facial swelling (facial oedema) or swelling of hands, feet and legs (peripheral oedema), weakness and fatigue (asthenia), general malaise, excessive drowsiness, chest pain, fever, pain
• Changes in liver enzyme levels (increased aspartate aminotransferase, increased alanine aminotransferase), changes in blood tests (increased blood bilirubin levels, increased blood urea levels, increased blood creatinine levels, abnormal blood potassium levels, increased alkaline phosphatase in blood, increased chloride, increased glucose, increased platelets, decreased haematocrit, increased bicarbonate, abnormal sodium levels)
• Complications following procedures

Rare

• Nervousness
• Abnormal liver function tests
• Increased sensitivity to sunlight

Not known

• Blood count changes, such as reduced platelet count (thrombocytopenia), which are essential for blood clotting, and abnormal breakdown of red blood cells (haemolytic anaemia), characterised by paleness, shortness of breath, headache, dizziness
• Aggressive behaviour, anxiety, delirium, hallucinations
• Fainting (syncope), seizures (fits), reduced skin sensitivity (hypoesthesia)
• Hyperactivity, loss of smell and taste, altered sense of smell, rapid muscle fatigue (myasthenia gravis)
• Hearing disorders including deafness and/or ringing in the ears (tinnitus)
• Heart rhythm disorders including increased heart rate (ventricular tachycardia); possible risk of electrocardiogram changes (QT interval prolongation and torsades de pointes), especially in patients predisposed to such changes (see "Warnings and precautions")
• Low blood pressure
• Discolouration of the tongue, inflammation of the pancreas (pancreatitis)
• Joint pain

Local reactions at the injection site (inflammation/pain) have been reported with intravenous administration of azithromycin.

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Azylung

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp".
The expiry date refers to the last day of that month.
Keep the vial in the outer packaging to protect the medicine from light.
Concentrated solution after reconstitution (according to instructions provided): azithromycin as a powder for solution for infusion is chemically and physically stable for 24 hours when stored at temperatures below 25°C.
Diluted solutions, prepared according to instructions provided, are chemically and physically stable for 24 hours at temperatures equal to or below 25°C, or for 7 days if stored refrigerated (5°C).
From a microbiological standpoint, the medicine should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C–8°C, unless reconstitution/dilution takes place under controlled and validated aseptic conditions.
Do not use this medicine if you notice any change in its appearance (e.g. the solution is not free from visible particles).
Unused medicine must be discarded.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Azylung contains

• The active substance is azithromycin (as dihydrate). Each vial contains 500 mg of azithromycin (equivalent to 524.0 mg of azithromycin dihydrate).
• The other components are: citric acid monohydrate and sodium hydroxide.

Description of the appearance of Azylung and contents of the pack
Azylung is a white to off-white powder for solution for infusion, with small aggregates. It is contained in a single-dose 15 ml clear glass vial sealed with a rubber stopper and an aluminium flip-off cap.
After reconstitution, the medicinal product is a clear, colourless solution without visible undissolved particles.
Azylung is available in the following pack sizes:
Pack of 1 vial.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
INCA-Pharm S.r.l.
Via Marittima, 38
03100 Frosinone
Manufacturers responsible for batch release
Sofarimex Indústria Química e Farmacêutica, S.A.
Av. das Indústrias - Alto do Colaride – Agualva
2735-213-Cacém
Portugal

This medicinal product is authorised in the European Economic Area countries under the following names:
Portugal: Azitromicina Biofarmoz, 500 mg, powder for solution for perfusion
Italy: Azylung

The following information is intended exclusively for healthcare professionals:

Azylung must be reconstituted and diluted as described in the instructions and administered as an intravenous infusion over a period of not less than 60 minutes.
Do not administer as a bolus or by intramuscular injection.
Azithromycin as a powder for solution for infusion is contained in a single-use vial.

Step 1: Preparation of the reconstituted solution
This medicinal product must be prepared under aseptic conditions.
The initial reconstituted solution is prepared by adding 4.4 ml of sterile water for injections to the contents of the 15 ml vial using a standard 5 ml (non-automated) syringe, and shaking the vial until the drug is completely dissolved. Each ml of reconstituted solution contains azithromycin dihydrate equivalent to 100 mg of azithromycin (100 mg/ml).
The reconstituted solution must be further diluted prior to use.

Step 2: Dilution of the reconstituted solution
To obtain an azithromycin solution with a concentration of 1.0 mg/ml:
transfer 5 ml of the azithromycin solution prepared in step 1 (100 mg/ml) into 500 ml of one of the suitable diluents listed below.

To obtain an azithromycin solution with a concentration of 2.0 mg/ml:
transfer 5 ml of the azithromycin solution prepared in step 1 (100 mg/ml) into 250 ml of one of the suitable diluents listed below.

The reconstituted solution may be diluted with:

• Sodium chloride 0.9%
• Sodium chloride 0.45%
• Dextrose 5% in water
• Ringer's lactate solution
• Dextrose 5% in sodium chloride 0.3%
• Dextrose 5% in sodium chloride 0.45%

Concentrated solution after reconstitution (as reported in the instructions): azithromycin as a powder for solution for infusion is chemically and physically stable for 24 hours when stored below 25°C.

Diluted solutions, prepared as described in the instructions, are chemically and physically stable for 24 hours at temperatures equal to or below 25°C, or for 7 hours if refrigerated (5°C).

From a microbiological standpoint, the product should be used immediately. If not used immediately, the in-use storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C–8°C, unless reconstitution/dilution has been carried out under controlled and validated aseptic conditions.

Parenteral medications should be visually inspected for particulate matter prior to administration. If particulate matter is observed, the reconstituted solution must be discarded.

Any unused medicinal product must be discarded.

No other intravenous substances, additives, or medicinal products should be added to Azylung or administered simultaneously through the same infusion line.