Azromax 250 mg film-coated tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
Azithromycin
Available from:
McDermott Laboratories Ltd., T/A Gerard Laboratories
ATC code:
J01FA; J01FA10
INN (International Name):
Azithromycin
Dosage:
250 milligram(s)
Pharmaceutical form:
Film-coated tablet
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Macrolides; azithromycin
Authorization status:
Marketed
Authorization number:
PA0577/122/001
Authorization date:
2010-06-04

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Package Leaflet: Information for the patient

Azromax 250mg Film-coated Tablets

azithromycin

Read all of this leaflet carefully before you start taking this medicine because it contains important

information for you

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if

their signs of illness are the same as yours.

If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not

listed in this leaflet. See section 4.

What is in this leaflet:

What Azromax is and what it is used for

What you need to know before you take Azromax

How to take Azromax

Possible side effects

How to store Azromax

Contents of the pack and other information

1. What Azromax is and what it is used for

Azromax is one of a group of antibiotics known as macrolides. It is used to treat bacterial infections caused

by microorganisms such as bacteria. These infections include:

Chest infections such as bronchitis and pneumonia

Infections in your sinuses, throat, tonsils or ears

Mild to moderate skin and soft tissue infections,

e.g.

infection of the hair follicles (folliculitis), bacterial

infection of the skin and its deeper layers (cellulitis), skin infection with shiny red swelling (erysipelas)

Infections caused by a bacterium called

Chlamydia trachomatis

. They can cause inflammation of the

tube that carries urine from your bladder (urethra) or where your womb joins your vagina (cervix).

2. What you need to know before you take Azromax

Do not take Azromax:

if you are allergic to azithromycin, any other macrolide (such as erythromycin or clarithromycin) or

ketolide antibiotic or any of the ingredients of this medicine (listed in section 6). An allergic reaction may

cause skin rash or wheezing.

Warnings and precautions

Talk to your doctor or pharmacist before taking Azromax if you:

have ever had a serious allergic reaction causing swelling of the face and throat, possibly with breathing

problems, rash, fever, swollen glands or increase in eosinophils (certain type of white blood cells).

have severe kidney problems: your doctor may alter the dose

have liver problems: your doctor may need to monitor your liver function or stop the treatment

have myasthenia gravis (localised muscle weakness)

have been diagnosed with a neurological disease, which is a disease of the brain or nervous system

have mental, emotional or behavioural problems

are taking medicines known as ergot alkaloids (such as ergotamine), which are used to treat migraine:

azithromycin is not recommended (see 'Other medicines and Azromax’ below)

Since azithromycin may increase the risk of abnormal heart rhythm please tell your doctor if you have any of

the following problems before taking this medicine (especially you are female or elderly):

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you are aware of ever being diagnosed to have prolonged QT interval (a heart condition, shown on an

electro-cardiogram or ECG machine): Azromax is not recommended

are aware that you have a slow or irregular heartbeat, or reduced heart function (heart failure): Azromax

is not recommended

know that you have low levels of potassium or magnesium in your blood: Azromax is not recommended

are taking medicines known as antiarrhythmics (e.g. quinidine, procainamide, dofetilide, amiodarone,

sotalol: used to treat abnormal heart rhythms), cisapride (used to treat stomach problems) or terfenadine

(an antihistamine that is used to treat allergies), or antipsychotic agents (e.g. pimozide), antidepressants

(e.g. citalopram), some antibiotics (e.g. moxifloxacin, levofloxacin) that can affect the heart rhythm:

Azromax is not recommended (see ‘Other medicines and Azromax below)

If you develop severe and persistent diarrhoea during or after treatment, especially if you notice blood or

mucus, tell your doctor immediately.

If your symptoms persist after the end of your treatment with Azromax, or if you notice any new and

persistent symptoms, contact your doctor.

Other medicines and Azromax

Tell your doctor

before

taking Azromax, if you are taking any of the medicines listed below:

Warfarin or any similar medicine to

prevent blood clots

: concomitant use can increase the risk of

bleeding.

Ergotamine, dihydroergotamine (used to treat

migraine

): ergotism (ie. itching in the limbs, muscle

cramps and gangrene of hands and feet due to poor blood circulation) may occur. Concomitant use is

therefore not recommended.

Ciclosporin (used to suppress the immune system to

prevent and treat rejection of an organ or bone

marrow transplant

): if concomitant use is required, your doctor will check your blood levels regularly

and may adapt the dose.

Digoxin (for

heart failure

): digoxin levels may increase. Your doctor will check your blood levels.

Colchicine (used for gout and familial Mediterranean fever).

Antacids (for

indigestion

): Azromax should be taken at least 1 hour before or 2 hours after the antacid.

Cisapride (for

stomach problems

), terfenadine (used to treat

hay fever

): concomitant use with

azithromycin may cause heart disorders.

Medicines for irregular heart beat (called

anti-arrythmics

), or to lower cholesterol (called

statins

) such

as atorvastatin.

Alfentanil (used for

narcosis

) or astemizole (used to treat

hay fever

): concomitant use with azithromycin

may increase the effect of these medicinal products.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your

doctor or pharmacist for advice before taking this medicine.

You should not use this medicine during pregnancy unless your doctor has specifically recommended it.

This medicine passes into human milk. You should talk to your doctor before taking this medicine if you are

breast-feeding.

Driving and using machines

Azromax may cause dizziness and fits. If affected, do not drive or operate machinery.

Azromax contains soya oil

If you are allergic to peanut or soya, do not use this medicinal product (see also section above ‘Do not take

Azromax’).

Azromax contains sodium.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

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3. How to take Azromax

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

Azromax tablets should be given as a single daily dose. The tablets should be swallowed preferably with a

drink of water, and can be taken with or without food.

The recommended dose is:

Adults (including older patients), children and adolescents with a body weight of over 45 kg:

The recommended dose is 1500 mg divided over either 3 or 5 days as follows:

When taken over 3 days, 500 mg once daily.

When taken over 5 days, 500 mg as a single dose on the first day and then 250 mg once daily on days 2

through to 5.

Inflammation of the urethra or cervix caused by Chlamydia: 1000 mg taken as a single dose, for one day

only.

For infections in your sinuses, treatment is indicated for adults and adolescents 16 years of age and over.

Children and adolescents with a body weight of 45 kg and under:

Tablets are not indicated for these patients. Other pharmaceutical forms of azithromycin-containing products

(e.g. suspensions) may be used.

Patients with kidney or liver problems:

You should tell your doctor if you have kidney or liver problems as your doctor may need to alter the normal

dose.

If you take more Azromax than you should

If you (or someone else) swallow a lot of the tablets altogether, or if you think a child has swallowed any of

the tablets, contact your doctor or pharmacist immediately. An overdose is likely to cause reversible hearing

loss, severe nausea (feeling sick), vomiting and diarrhoea.

Please take this leaflet, any remaining tablets and the container with you to the hospital or doctor so that they

know which tablets were consumed.

If you forget to take Azromax

If you forget to take a tablet, take one as soon as you remember, unless it is nearly time to take the next one.

Do not take a double dose to make up for a forgotten dose.

If you stop taking Azromax

Do not stop taking your medicine without talking to your doctor first even if you feel better. It is very

important that you keep taking Azromax for as long as your doctor has told you to; otherwise the infection

may come back.

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

4. Possible side effects

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

If the following happens, stop taking the tablets and tell your doctor immediately or go to the casualty

department at your nearest hospital:

Uncommon (may affect up to 1 in 100 people):

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a severe skin reaction causing blisters/bleeding of the lips, eyes, nose, mouth and genitals (Stevens-

Johnson syndrome).

yellowing of the skin and whites of the eyes, tiredness and loss of appetite which may be caused by

inflammation of the liver (hepatitis).

Rare (may affect up to 1 in 1,000 people):

yellowing of the skin or eyes (jaundice)

skin eruption that is characterised by the rapid appearance of areas of red skin studded with small pustules

(small blisters filled with white/yellow fluid).

Very rare (may affect up to 1 in 10,000 people):

skin rash accompanied by other symptoms such as fever, swollen glands and an increase of eosinophils (a

type of white blood cell).

Not known (frequency cannot be estimated from the available data):

an allergic reaction (swelling of the lips, face or neck leading to severe difficulty in breathing; skin rash or

hives).

severe peeling of the skin or an itchy rash with pink-red rings around a pale centre (toxic epidermal

necrolysis, erythema multiforme).

disturbances in heart rhythm called QT prolongation (delayed conduction of electrical signals which can

be seen on an ECG, an electrical recording of the heart). In some people this can develop into a

potentially serious heart condition known as Torsades de pointes. This can result in a very fast heartbeat

causing a sudden loss of consciousness

an irregular heart beat

feeling weak and breathless with yellowing of the skin which may be due to a reduced number of red

blood cells due to destruction (haemolytic anaemia)

prolonged diarrhoea with blood and mucus

stomach pain that moves to the back with feeling and being sick which may be caused by inflammation of

the pancreas (pancreatitis)

pain in the middle of the back and problems passing water, inflammation of the kidney or kidney failure

pain in the upper right of the stomach with feeling and being sick, swelling of the stomach yellowing of

the skin and eyes which may be due to liver failure (rarely life-threatening)

fits.

These are very serious side effects. You may need urgent medical attention or hospitalisation.

The following side effects have been reported:

Very common (may affect more than 1 in 10 people):

diarrhoea

feeling sick

abdominal pain

flatulence (wind)

Common (may affect up to 1 in 10 people):

headache

dizziness, feeling drowsy (somnolence), taste disturbance, numbness or pins and needles (paraesthesia)

visual disturbances

deafness

being sick

indigestion

skin rash

itching

joint pain (arthralgia)

tiredness

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changes in white blood cell count in blood tests

low blood bicarbonate

Uncommon (may affect up to 1 in 100 people):

reduced sense of touch or sensation (hypoaesthesia)

changes in liver function

skin more sensitive to light than normal

yeast infections of the mouth and vagina (thrush), vaginal infections, fungal infections, bacterial

infections, inflammation of the throat, inflammation of the stomach and intestine, breathing difficulties,

runny or blocked nose

allergic reactions of various severity

loss of appetite

feeling nervous

sleeplessness (insomnia)

ear disorder, vertigo

hearing impairment including hearing loss

tinnitus (ringing in your ears)

heart palpitations

hot flushes

recurring frequent infections with fever, chills, sore throat, mouth ulcers, which may be caused by a

decrease in the number of white cells in the blood.

serious lung infection with symptoms such as fever, chills, shortness of breath, cough and phlegm

(pneumonia)

general swelling

nose bleeds

constipation, inflammation of the lining of the stomach (gastritis), difficulty swallowing, feeling bloated,

dry mouth, belching, mouth ulceration, saliva increased

hives, inflammation of the skin (dermatitis), dry skin, increased sweating

bone and joint pain, muscle pain, back pain, neck pain

pain when passing urine, kidney pain

abnormal or unexpected bleeding from the vagina

problems with your testicles

general loss of strength, generally feeling unwell, swelling of the face, chest pain, fever, pain, swelling of

the lower limbs

abnormal laboratory test values (e.g. blood or liver tests)

post procedural complication

shortness of breath

Rare (may affect up to 1 in 1,000 people):

agitation

irritability

Not known (frequency cannot be estimated from the available data):

blood taking longer to clot and bruising more easily which may be due to a reduction in number of

platelets (thrombocytopenia)

aggression, anxiety, severe confusion (delirium), seeing, feeling or hearing things that are not there

(hallucination)

fainting, feeling hyperactive, loss of smell or altered sense of smell, loss of taste

muscle weakness or worsening of muscle weakness (myasthenia gravis)

low blood pressure

tongue discolouration

tooth discolouration

The following side effects have been reported in prophylactic treatment against Mycobacterium Avium

complex (MAC):

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Very common (may affect more than 1 in 10 people):

diarrhoea

abdominal pain

feeling sick

wind

abdominal discomfort

loose stools

Common (may affect up to 1 in 10 people):

loss of appetite

dizziness

headache

numbness or pins and needles (paraesthesia)

taste disturbance

visual disturbances

deafness

skin rash and/or itching

joint pain

tiredness

Uncommon (may affect up to 1 in 100 people):

reduced sense of touch or sensation (hypoaesthesia)

poor hearing or ringing in the ears

heart palpitations

skin more sensitive to sunlight than normal

general loss of strength

generally feeling unwell

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed

in this leaflet. You can also report side effects directly via HPRA Pharmacovigilance website: www.hpra.ie.

By reporting side effects you can help provide more information on the safety of this medicine.

5.

How to store Azromax

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

This medicinal product does not require any special storage conditions. Do not transfer the tablets to another

container. Do not use this medicine after the expiry date, which is stated on the carton and blister after EXP.

The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw

away medicines you no longer use. These measures will help protect the environment.

6. Content of the pack and other information

What Azromax film-coated tablet contains

The active substance is azithromycin.

Each tablet contains 250 mg of the active ingredient azithromycin (as azithromycin monohydrate).

The other ingredients (excipients) are: microcrystalline cellulose (E460), pregelatinised maize starch,

sodium starch glycolate (Type A), anhydrous colloidal silica (E551), sodium lauryl sulphate, magnesium

stearate (E470b), Tablet Film-coating ingredients are: polyvinyl alcohol (partially hydrolysed), titanium

dioxide (E171), talc (E553b), soya lecithin (see “Azromax contains soya oil”) and xanthan gum (E 415).

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What Azromax Film-coated tablets looks like and contents of the pack

Azromax 250 mg tablets are white to off-white, oblong film-coated tablets and plain on both sides.

The 250 mg tablets are available in pack sizes of 4, 6, 12, 24, 50 or 100 tablets in blister strips.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

McDermott Laboratories Limited t/a Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange Road,

Dublin 13, Ireland

Manufacturer

McDermott Laboratories Limited t/a Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange Road,

Dublin 13, Ireland

Sandoz GmbH, Biochemiestraße 10, 6250 Kundl, Austria

Sandoz S.R.L, Livezeni Street no 7A, 540472 Targu Mures, Romania

Generics UK Limited, Station Close, Potters Bar, Hertfordshire, EN6 1TL, United Kingdom

This medicinal product is authorised in the Member States of the EEA under the following names:

Austria

‘Azithromycin Arcana 500 mg Filmtabletten’

Belgium

‘Azithromycine Mylan 250 mg & 500 mg filmomhulde tabletten’

Czech Republic ‘

‘Azitromycin Mylan 500 mg potahovane tablety’

Denmark

‘Azithromycin Mylan’

Ireland

‘Azromax 250 mg Film-coated Tablets’

Italy

‘Azitromicina Mylan’

The Netherlands

‘Azitromycine Mylan 250 mg & 500mg filmomhulde tabletten’

Poland

‘Azigen’

Portugal

‘Azitromicina Anova’

Slovakia

‘Azitromycin Mylan 500 mg’

Sweden

‘Azithromycin Mylan 250 mg & 500 mg filmdragerad tablett’

United Kingdom

‘Azithromycin 250 mg & 500 mg Film-Coated Tablets’

This leaflet was last revised in October 2019.

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Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Azromax 250mg Film-coated Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains 250 mg azithromycin (as azithromycin monohydrate).

Excipients with known effect:

Each film-coated tablet contains 0.18 mg of soya lecithin.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet.

Azithromycin 250 mg Film-coated Tablets are white to off-white, oblong film-coated tablets and plain on both sides.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Azithromycin is indicated for the treatment of the following infections, when caused by microorganisms sensitive to

azithromycin (see section 4.4 and 5.1):

Acute bacterial sinusitis (adequately diagnosed)

Acute bacterial otitis media (adequately diagnosed)

Pharyngitis, tonsillitis

Acute exacerbation of chronic bronchitis (adequately diagnosed)

Mild to moderately severe community acquired pneumonia

Infections of the skin and soft tissues of mild to moderate severity e.g. folliculitis, cellulitis, erysipelas

Uncomplicated Chlamydia trachomatis urethritis and cervicitis

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration

Posology

Azithromycin tablets should be given as a single daily dose. The duration of treatment in each of the infectious diseases is

given below.

Adults, elderly, children and adolescents over 45 kg body weight

The total dosage of azithromycin is 1500 mg which is spread over three days (500 mg once daily).

Alternatively, the dosage can be spread over five days (500 mg as a single dose on the first day and thereafter 250 mg once

daily).

In uncomplicated Chlamydia trachomatis urethritis and cervicitis the dosage is 1000 mg as a single oral dose.

For sinusitis, treatment is indicated for adults and adolescents 16 years of age and over.

Children and adolescents 45 kg and under body weight

Tablets are not indicated for these patients. Other pharmaceutical forms of azithromycin, e.g. suspensions may be used.

Elderly

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No dose adjustments are required for elderly patients. Since elderly patients can be patients with ongoing proarrhythmic

conditions a particular caution is recommended due to the risk of developing cardiac arrhythmia and torsades de pointes (see

section 4.4).

Patients with renal impairment

No dose adjustment is necessary in patients with mild to moderate renal impairment (GFR 30-80 ml/min/1.73 m

) (see section

4.4).

Patients with hepatic impairment

A dose adjustment is not necessary for patients with mild to moderately impaired liver function (Child-Pugh class A or B) (see

section 4.4).

Method of administration

For oral use.

The tablets can be taken with or without food.

4.3 Contraindications

Hypersensitivity to the active substance, to erythromycin or any macrolide or ketolide antibiotic or to any of the excipients

listed in section 6.1.

4.4 Special warnings and precautions for use

Allergic reactions

As with erythromycin and other macrolides, rare serious allergic reactions including angioneurotic oedema and anaphylaxis

(rarely fatal) have been reported alongside dermatological reactions, including acute generalised exanthematous pustulosis

(AGEP), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (rarely fatal) and DRESS syndrome (Drug Reaction

with Eosinophilia and Systemic Symptoms). A certain number of these reactions resulted in recurring symptoms and required

an extended period of observation and treatment.

If an allergic reaction occurs, use of this medicinal product must be discontinued and the appropriate treatment initiated.

Doctors must be aware that allergic symptoms can recur if symptomatic treatment is discontinued.

Renal impairment

No dose adjustment is necessary in patients with mild to moderate renal impairment (creatinine clearance > 40 ml/min). In

patients with severe renal function impairment (GFR < 10 mL/min), a 33% increase in systemic exposure to azithromycin has

been observed (see section 5.2).

Hepatic impairment

Since liver is the principal route of elimination for azithromycin, the use of azithromycin should be undertaken with caution in

patients with significant hepatic disease. Cases of fulminant hepatitis potentially leading to life-threatening liver failure have

been reported with azithromycin (see section 4.8). Some patients may have or have had pre-existing hepatic disease or may

have been taking other hepatotoxic medicinal products.

In case of signs and symptoms of liver dysfunction, such as rapid developing asthenia associated with jaundice, dark urine,

bleeding tendency or hepatic encephalopathy, liver function tests/ investigations should be performed immediately.

Azithromycin administration should be stopped if liver dysfunction has emerged.

Liver function disorders, hepatitis, cholestatic jaundice, liver necrosis and renal failure have been reported and have been fatal

in a number of cases. Discontinue the use of azithromycin if signs and symptoms of hepatitis occur.

Pseudomembranous colitis has been reported following use of macrolide antibiotics. This diagnosis should therefore be taken

into consideration in patients who develop diarrhoea after starting treatment with azithromycin.

Infantile hypertrophic pyloric stenosis

Following the use of azithromycin in neonates (treatment up to 42 days of life), infantile hypertrophic pyloric stenosis (IHPS)

has been reported. Parents and caregivers should be informed to contact their physician if vomiting or irritability with feeding

occurs.

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Ergot alkaloids and azithromycin

The concurrent use of ergot alkaloids and macrolide antibiotics has been found to accelerate the development of ergotism.

The interactions between ergot alkaloids and azithromycin have not been studied. The development of ergotism is however

possible, so that azithromycin and ergot alkaloid derivatives should not be administered simultaneously.

QT prolongation

Prolonged cardiac repolarisation and a prolonged QT interval, imparting a risk of developing cardiac arrhythmia and torsades

de pointes, have been seen in treatment with other macrolides including azithromycin (see section 4.8).

Therefore, as the following situations may lead to an increased risk for ventricular arrhythmias (including torsade de pointes)

which can lead to cardiac arrest, azithromycin should be used with caution in patients with ongoing proarrhythmic conditions

(especially women and elderly patients) such as:

Patients with congenital or documented acquired QT prolongation.

Patients currently receiving treatment with other active substances that prolong QT interval such as

antiarrhythmics of class IA (quinidine and procainamide) and class III (dofetilide, amiodarone and sotalol), cisapride

and terfenadine; antipsychotic agents such as pimozide; antidepressants such as citalopram; and fluoroquinolones

such as moxifloxacin and levofloxacin (see section 4.5).

Patients with a disrupted electrolyte balance, particularly in cases of hypokalaemia and hypomagnesaemia

Patients with clinically relevant bradycardia, cardiac arrhythmia or severe cardiac insufficiency.

Myasthenia gravis and azithromycin

Exacerbations of the symptoms of myasthenia gravis and new onset of myasthenia syndrome have been reported in patients

receiving azithromycin therapy (see section 4.8).

Superinfections

As with any antibiotic preparation, observation for signs of superinfection with non-susceptible organisms, including fungi is

recommended.

Clostridium difficile associated diarrhoea

Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including

azithromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the

normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile

cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require

colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical

history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

The following should be considered before prescribing azithromycin:

Azithromycin film-coated tablets are not suitable for treatment of severe infections where a high concentration of the antibiotic

in the blood is rapidly needed.

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As for other macrolides, high resistance rates of Streptococcus pneumoniae have been reported for azithromycin in some

European countries (see section 5.1). This should be taken into account when treating infections caused by Streptococcus

pneumoniae.

The main causative agent of soft tissue infections, Staphylococcus aureus, is frequently resistant to azithromycin. Therefore,

susceptibility testing is considered a precondition for treatment of soft tissue infections with azithromycin.

Pharyngitis/tonsillitis

Azithromycin is not the substance of first choice for the treatment of pharyngitis and tonsillitis caused by Streptococcus

pyogenes. For this and for the prophylaxis of acute rheumatic fever penicillin is the treatment of first choice.

Sinusitis

Often, azithromycin is not the substance of first choice for the treatment of sinusitis.

Acute otitis media

Often, azithromycin is not the substance of first choice for the treatment of acute otitis media.

Infected burn wounds

Azithromycin is not indicated for the treatment of infected burn wounds.

Sexually transmitted disease

In case of sexually transmitted diseases a concomitant infection by T. pallidum should be excluded.

Neurological or psychiatric diseases

Azithromycin should be administered with caution to patients suffering from neurological or psychiatric diseases.

Long-term use

There is no experience regarding the safety and efficacy of long-term use of azithromycin for the mentioned indications. In

case of rapid recurrent infections, treatment with another antibiotic should be considered.

Due to cross-resistance existing among macrolides, in areas with a high incidence of erythromycin resistance, it is especially

important to take into consideration the evolution of the pattern of susceptibility to azithromycin and other macrolides (see

section 5.1).

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Azithromycin is not the first choice for the empirical treatment of infections in areas where the prevalence of resistant isolates

is 10% or more (see section 5.1).

Paediatric population

Safety and efficacy for the prevention or treatment of Mycobacterium Avium Complex in children

have not been established.

This medicinal product contains soya oil

Azithromycin contains soya oil. Patients who are allergic to peanut or soya, must not use this medicinal product.

Azithromycin contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.

4.5 Interaction with other medicinal products and other forms of interactions

Antacids

When studying the effect of simultaneously administered antacid on the pharmacokinetics of azithromycin, no overall change

has been observed in the bioavailability, although the peak concentrations of azithromycin measured in the plasma reduced by

approximately 25 %. In patients receiving both azithromycin and antacids, the drugs should not be taken simultaneously.

Azithromycin should be taken at least 1 hour before or 2 hours after the antacid.

Cetirizine

In healthy volunteers, co-administration of a 5-day regimen of azithromycin with cetirizine 20 mg at steady-state resulted in no

pharmacokinetic interaction and no significant changes in the QT interval.

Didanosine (Dideoxyinosine)

Co-administration of 1200 mg/day azithromycin with 400 mg/day didanosine in 6 HIV-positive subjects did not appear to

affect the steady-state pharmacokinetics of didanosine as compared with placebo.

Digoxin and colchicine (P-gp substrates)

Concomitant administration of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin

and colchicine, has been reported to result in increased serum levels of the P-glycoprotein substrate. Therefore, if azithromycin

and P-gp substrates such as digoxin are administered concomitantly, the possibility of elevated serum concentrations of the

substrate should be considered. During treatment with azithromycin and after discontinuation, clinical monitoring, and possible

follow-up of serum digoxin levels, is required.

Zidovudine

Single 1000 mg doses and multiple 1200 mg or 600 mg doses of azithromycin had little effect on the plasma pharmacokinetics

or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of azithromycin increased the

concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The

clinical significance of this finding is unclear, but it may be of benefit to patients.

Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not believed to undergo the

pharmacokinetic drug interactions as seen with erythromycin and other macrolides. Hepatic cytochrome P450 induction or

inactivation via cytochrome-metabolite complex does not occur with azithromycin.

Ergot derivatives

Due to the theoretical possibility of ergotism, the concurrent use of azithromycin with ergot derivatives is not recommended

(see section 4.4).

Pharmacokinetic studies have been conducted between azithromycin and the following medicinal products known to undergo

significant cytochrome P450 mediated metabolism.

Astemizole and alfentanil

No data are available on interactions with astemizole and alfentanil. Caution should be exercised with concomitant use of these

agents and azithromycin in view of the described potentiation of its effect during concomitant use of the macrolide antibiotic

erythromycin.

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Atorvastatin

Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter the plasma concentrations of

atorvastatin (based on a HMG CoA-reductase inhibition assay). However, post-marketing cases of rhabdomyolysis in patients

receiving azithromycin with statins have been reported.

Carbamazepine

In a pharmacokinetic interaction study in healthy volunteers, no significant effect was observed on the plasma levels of

carbamazepine or its active metabolite in patients receiving concomitant azithromycin.

Cisapride

Cisapride is metabolised in the liver by the enzyme CYP 3A4. Because macrolides inhibit this enzyme, concomitant

administration of cisapride may cause the increase of QT interval prolongation, ventricular arrhythmias and torsades de pointes.

Cimetidine

In a pharmacokinetic study investigating the effects of a single dose of cimetidine, given 2 hours before azithromycin, on the

pharmacokinetics of azithromycin, no alteration of azithromycin pharmacokinetics was seen.

Coumarin-Type Oral Anticoagulants

In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin

administered to healthy volunteers. There have been reports received in the post-marketing period of potentiated

anticoagulation subsequent to co-administration of azithromycin and coumarin type oral anticoagulants. Although a causal

relationship has not been established, consideration should be given to the frequency of monitoring prothrombin time when

azithromycin is used in patients receiving coumarin-type oral anticoagulants.

Ciclosporin

In a pharmacokinetic study with healthy volunteers that were administered a 500 mg/day oral dose of azithromycin for 3 days

and were then administered a single 10 mg/kg oral dose of ciclosporin, the resulting ciclosporin C

and AUC0-5 were found

to be significantly elevated. Consequently, caution should be exercised before considering concurrent administration of these

medicinal products. If co-administration of these medicinal products is necessary, ciclosporin levels should be monitored and

the dose adjusted accordingly.

Efavirenz

Co-administration of a 600 mg single dose of azithromycin and 400 mg efavirenz daily for 7 days did not result in any clinically

significant pharmacokinetic interactions.

Fluconazole

Co-administration of a single dose of 1200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg

fluconazole. Total exposure and half-life of azithromycin were unchanged by the coadministration of fluconazole, however, a

clinically insignificant decrease in C

(18%) of azithromycin was observed.

Indinavir

Co-administration of a single dose of 1200 mg azithromycin had no statistically significant effect on the pharmacokinetics of

indinavir administered as 800 mg three times daily for 5 days.

Methylprednisolone

In a pharmacokinetic interaction study in healthy volunteers, azithromycin had no significant effect on the pharmacokinetics of

methylprednisolone.

Midazolam

In healthy volunteers, co-administration of azithromycin 500 mg/day for 3 days did not cause clinically significant changes in

the pharmacokinetics and pharmacodynamics of a single 15 mg dose of midazolam.

Nelfinavir

Co-administration of azithromycin (1200 mg) and nelfinavir at steady state (750 mg three times daily) resulted in increased

azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment is required.

Rifabutin

Co-administration of azithromycin and rifabutin did not affect the serum concentrations of either active.

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Neutropenia was observed in subjects receiving concomitant treatment of azithromycin and rifabutin. Although neutropenia

has been associated with the use of rifabutin, a causal relationship to combination with azithromycin has not been established

(see section 4.8).

Sildenafil

In normal healthy male volunteers, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC

and C

, of sildenafil or its major circulating metabolite.

Terfenadine

Pharmacokinetic studies have reported no evidence of an interaction between azithromycin and terfenadine. There have been

rare cases reported where the possibility of such an interaction could not be entirely excluded; however there was no specific

evidence that such an interaction had occurred.

Theophylline

There is no evidence of a clinically significant pharmacokinetic interaction when azithromycin and theophylline are

co-administered to healthy volunteers.

Triazolam

In 14 healthy volunteers, co-administration of azithromycin 500 mg on Day 1 and 250 mg on Day 2 with 0.125 mg triazolam on

Day 2 had no significant effect on any of the pharmacokinetic variables for triazolam compared to triazolam and placebo.

Trimethoprim/sulfamethoxazole

Co-administration of trimethoprim/sulfamethoxazole DS (160 mg/800 mg) for 7 days with azithromycin 1200 mg on Day 7 had

no significant effect on peak concentrations, total exposure or urinary excretion of either trimethoprim or sulfamethoxazole.

Azithromycin serum concentrations were similar to those seen in other studies.

Protease inhibitors

There are no data available about a possible interaction with protease inhibitors.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no adequate and well-controlled studies on the use of azithromycin in pregnant women. Published studies with

retrospectively collected data do not indicate up to now an increased risk of congenital malformations. In reproduction toxicity

studies in animals, azithromycin was shown to cross the placenta, but no teratogenic effects were observed. The safety of

azithromycin has not been confirmed with regard to the use of the active substance during pregnancy. Therefore, azithromycin

should only be used during pregnancy if the benefit outweighs the risk.

Breast-feeding

Azithromycin is excreted in breast milk.

Because of the long half-life, accumulation in the milk is possible. Information available from published literature indicates that,

in short-term use, this does not lead to clinically relevant quantities in the milk. No serious side effects have been observed by

azithromycin in breast-fed children. A decision should be taken whether breastfeeding is discontinued or that treatment with

azithromycin is discontinued/initiated or not, taking into account the benefit of breastfeeding for the child and the benefit of

treatment for the woman.

Fertility

In fertility studies conducted in rat, reduced pregnancy rates were noted following administration of azithromycin. The

relevance of this finding to humans is unknown.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. However, the possibility of

undesirable effects like dizziness and convulsions should be taken into account when performing these activities.

4.8 Undesirable effects

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The table below lists the adverse reactions identified through clinical trial experience and post-marketing surveillance by

system organ class and frequency. The frequency grouping is defined using the following convention: Very common (≥1/10);

Common (≥ 1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥ 1/10,000 to <1/1,000); Very Rare (< 1/10,000); and Not

known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in

order of decreasing seriousness.

Adverse reactions possibly or probably related to azithromycin based on clinical trial experience and post-marketing

surveillance:

Very

Common

Common

Uncommon

Rare

Very rare

Not Known

Infections and

Infestations

Candidiasis,

vaginal infection,

pneumonia,

fungal infection,

bacterial

infection,

pharyngitis,

gastroenteritis,

respiratory

disorder, rhinitis,

oral candidiasis

Pseudomembranous

colitis (see section 4.4)

Blood and

Lymphatic

System

Disorders

Leukopenia,

neutropenia,

eosinophilia

Thrombocytopenia,

haemolytic anaemia

Immune System

Disorders

Angioedema,

hypersensitivity

Anaphylactic reaction

(see section 4.4)

Metabolism and

Nutrition

Disorders

Anorexia

Psychiatric

Disorders

Nervousness,

insomnia

Agitation,

irritability

Aggression, anxiety,

delirium, hallucination

Nervous System

Disorders

Headache,

dizziness,

somnolence,

dysgeusia,

paraesthesia

Hypoaesthesia

Syncope, convulsion,

psychomotor

hyperactivity, anosmia,

ageusia, parosmia,

myasthenia gravis (see

section 4.4)

Eye Disorders

Visual

impairment

Ear and

Labyrinth

Disorders

Deafness

Ear disorder,

vertigo, hearing

impairment

including hearing

loss, tinnitus

Cardiac

Disorders

Palpitations

Torsades de pointes

(see section 4.4),

arrhythmia (see section

4.4) including

ventricular tachycardia,

Electrocardiogram QT

prolonged (see section

4.4)

Vascular

Disorders

Hot flushes

Hypotension

Respiratory,

thoracic and

mediastinal

Dyspnoea,

epistaxis

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disorders

Gastrointestinal

Disorders

Diarrhoea,

abdominal

pain,

nausea,

flatulence

Vomiting,

dyspepsia

Constipation,

gastritis,

dysphagia,

abdominal

distension, dry

mouth,

eructation,

mouth ulceration,

salivary

hypersecretion

Pancreatitis, tongue

discolouration, tooth

discolouration

Hepatobiliary

Disorders

Hepatitis,

abnormal hepatic

function

Cholestatic

jaundice

Hepatic failure (which

has rarely resulted in

death) (see section 4.4),

fulminant hepatitis,

hepatic necrosis

Skin and

Subcutaneous

Tissue Disorders

Rash,

pruritus

Urticaria,

dermatitis, dry

skin,

hyperhidrosis,

Stevens-Johnson

syndrome,

Photosensitivity

reaction

Acute

generalised

exanthematous

pustulosis

(AGEP)

DRESS

syndrome

(Drug

Reaction

with

Eosinophilia

Systemic

Symptoms)

Toxic epidermal

necrolysis, erythema

multiforme

Musculoskeletal

and Connective

Tissue Disorders

Arthralgia

Osteoarthritis,

myalgia, back

pain, neck pain

Renal and

Urinary

Disorders

Dysuria, renal

pain

Acute renal failure,

interstitial nephritis

Reproductive

system and

breast disorders

Metrorrhagia,

testicular disorder

General

Disorders and

Administration

Site Conditions

Fatigue

Oedema,

asthenia, malaise,

face oedema,

chest pain,

pyrexia, pain,

peripheral

oedema

Investigations

Lymphocyte

count

decreased,

eosinophil

count

increased,

blood

bicarbonate

decreased,

basophils

increased,

monocytes

increased,

neutrophils

increased

Aspartate

aminotransferase

increased, alanine

aminotransferase

increased, blood

bilirubin

increased, blood

urea increased,

blood creatinine

increased, blood

potassium

abnormal, blood

alkaline

phosphatase

increased,

chloride

increased,

glucose

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increased,

platelets

increased,

haematocrit

decreased,

bicarbonate

increased,

abnormal sodium

Injury,

poisoningand

procedural

complications

Post procedural

complication

Adverse reactions possibly or probably related to Mycobacterium Avium Complex prophylaxis and treatment based on clinical

trial experience and post-marketing surveillance. These adverse reactions differ from those reported with immediate release or

the prolonged release formulations, either in kind or in frequency:

Very Common

Common

Uncommon

Metabolism and

Nutrition

Disorders

Anorexia

Nervous System

Disorders

Dizziness,

headache,

paraesthesia,

dysgeusia

Hypoaesthesia

Eye Disorders

Visual

impairment

Ear and

Labyrinth

Disorders

Deafness

Hearing

impaired,

tinnitus

Cardiac

Disorders

Palpitations

Gastrointestinal

Disorders

Diarrhoea, abdominal pain, nausea, flatulence, abdominal discomfort,

loose stools

Hepatobiliary

Disorders

Hepatitis

Skin and

Subcutaneous

Tissue Disorders

Rash,

pruritus

Stevens-Johnson

syndrome,

photosensitivity

reaction

Musculoskeletal

and Connective

Tissue Disorders

Arthralgia

General

Disorders and

Administration

Site Conditions

Fatigue

Asthenia,

malaise

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued

monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected

adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517.

Website: www.hpra.ie; E-mail:medsafety@hpra.ie.

4.9 Overdose

Adverse events experienced in higher than recommended doses were similar to those seen at normal doses. Characteristic

symptoms of overdose with macrolide antibiotics include the following: reversible hearing loss, severe nausea, vomiting and

diarrhoea

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