Azithromycin 3's 500mg tablets

1. Name of the medicinal product
Azithromycin 500 mg Tablets

2. Qualitative and quantitative composition
Each film-coated tablet contains: 500 mg of azithromycin (as monohydrate)

Excipient(s) with known effect:

Each tablet contains 0.36 mg soya lecithin.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form
Film-coated tablet

White to off-white, oblong, film-coated tablet, deep break line on one side and score line on other side. The tablet can be divided into equal doses.

4. Clinical particulars
4.1 Therapeutic indications
Azithromycin tablets can be applied for the treatment of the following infections, when caused by microorganisms sensitive to azithromycin (see sections 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

- skin and soft tissue infections

- uncomplicated Chlamydia trachomatis urethritis and cervicitis

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

4.2 Posology and method of administration
Posology

Adults

In uncomplicated Chlamydia trachomatis urethritis and cervicitis the dose is 1,000 mg as a single oral dose.

For all other indications the dose is 1,500 mg, to be administered as 500 mg per day for three consecutive days. As an alternative the same total dose (1,500 mg) can also be administered over a period of five days with 500 mg on the first day and 250 mg on the second to the fifth day.

Elderly people

The same dose as in adult patients is used for older people. Since elderly people 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).

Paediatric population

Azithromycin tablets should only be administered to children weighing more than 45 kg when normal adult dose should be used. For children under 45 kg other pharmaceutical forms of azithromycine, e.g. suspensions, may be used.

In patients with renal impairment: No dose adjustment is necessary in patients with mild to moderate renal impairment (GFR 10-80 ml/min) (see section 4.4).

In patients with hepatic impairment: A dose adjustment is not necessary for patients with mild to moderately impaired liver function (see section 4.4).

Method of administration

Azithromycin Tablets should be given as a single daily dose. The tablets may be taken with food.

4.3 Contraindications
Hypersensitivity to the active substance, erythromycin, any macrolide or ketolide antibiotic, soya lecithin or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use
Hypersensitivity

As with erythromycin and other macrolides, rare serious allergic reactions including angioneurotic oedema and anaphylaxis (rarely fatal), dermatologic reactions including acute generalised exanthematous pustulosis (AGEP), Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (rarely fatal) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. Some of these reactions with azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment.

If an allergic reaction occurs, the medicinal product should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.

Hepatoxicity

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 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.

Abnormal liver function, hepatitis, cholestatic jaundice, hepatic necrosis, and hepatic failure have been reported, some of which have resulted in death. Discontinue azithromycin immediately if signs and symptoms of hepatitis occur.

Infantile hypertrophic pyloric stenosis (IHPS)

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.

Pseudomembranous colitis

Pseudomembranous colitis has been reported with the use of macrolide antibiotics. This diagnosis should therefore be considered in patients who get diarrhoea after starting treatment with azithromycin.

Ergot derivatives

In patients receiving ergotamine derivatives, ergotism has been precipitated by coadministration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergotamine derivatives and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin and ergot derivatives should not be co-administered (see section 4.5).

Cross resistance

Cross-resistance exists between azithromycin and other macrolides (erythromycin, clarithromycin, roxithromycin), lincosamides and streptogramin B (MLSB phenotype). Concomitant use of several medicinal products from the same or related group of antibacterial agents is not recommended.

Cardiovascular events

Prolonged cardiac repolarisation and 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 arrhytmias (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 QT prolongation.

- Currently receiving treatment with other active substances known to 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

- With electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesaemia

- With clinically relevant bradycardia, cardiac arrhythmia or severe cardiac insufficiency.

Epidemiological studies investigating the risk of adverse cardiovascular outcomes with macrolides have shown variable results. Some observational studies have identified a rare short term risk of arrhythmia, myocardial infarction and cardiovascular mortality associated with macrolides including azithromycin. Consideration of these findings should be balanced with treatment benefits when prescribing azithromycin.

Clostridoides difficile associated diarrhoea

Clostridoides difficile associated diarrhoea (CDAD) has been reported with the 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 infec