Azithromycin is indicated for the following bacterial infections induced by micro-organisms susceptible to
azithromycin (see sections 4.4 and 5.1):
- Acute bacterial sinusitis (adequately diagnosed)
- Acute bacterial otitis media (adequately diagnosed)
- Pharyngitis, tonsillitis (see section 4.4 regarding streptococcal infections)
- 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.

Posology
Azithromycin should be given as a single daily dose. Duration of the treatment for the different infection
diseases is given below.
Adults, children and adolescents with a body weight of 45 kg or over:
The total dose is 1500 mg, administered as 500 mg once daily for 3 days. Alternatively, the same total
dose (1500 mg) can be administered in a period of 5 days, 500 mg on the first day and 250 mg on day 2
to 5.
In the case of uncomplicated Chlamydia trachomatis urethritis and cervicitis, the dosage is 1000 mg as a
single oral dose.
For patients who are allergic to penicillin and/or cephalosporins, prescribers should consult local treatment
guidelines.
Children and adolescents with a body weight below 45 kg:
Azithromycin tablets are not suitable for patients under 45 kg body weight. Other dosage forms are
available for this group of patients.
Elderly patients
For elderly patients the same dose as for adults can be applied. 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:
Dose adjustment is not required in patients with mild to moderate renal impairment (GFR 10-80 ml/min).
Caution should be exercised when azithromycin is administered to patients with severe renal impairment
(GFR < 10 ml/min) (see section
4.4 and section 5.2).
Patients with hepatic impairment:
Since azithromycin is metabolised in the liver and excreted in the bile, the drug should not be given to
patients suffering from severe liver disease. No studies have been conducted regarding treatment of such
patients with azithromycin (see section 4.4).
Method of administration
Azithromycin Film-coated Tablets are for oral administration only. The tablets can be taken with or without
food. The tablets should be taken with ½ glass of water.

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 drug 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.
Hepatotoxicity
Since the 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.
Ergot derivatives
In patients receiving ergot derivatives, ergotism has been precipitated by co-administration 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).
Prolongation of the QT interval
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. A similar effect with
azithromycin cannot be completely ruled out in patients at increased risk for prolonged cardiac
repolarisation (see section 4.8); therefore caution is required when treating patients:

- With congenital or documented QT prolongation.
- Currently receiving treatment with other active substances known to prolong QT interval such as
antiarrhythmics of classes Ia and III, cisapride and terfenadine.
- With electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesaemia
- With clinically relevant bradycardia, cardiac arrhythmia or severe cardiac
insufficiency.
- Superinfection:
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 the use of nearly all
antibacterial agents, including azithromycin, and may range in severity from mild diarrhoea to fatal
colitis.
Strains of C. difficile producing hypertoxins A and B 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. Therefore, CDAD must be considered in
patients who present with diarrhoea during or subsequent to the administration of any antibiotics. Careful
medical history is necessary since CDAD has been reported to occur over two months after the
administration of antibacterial agents. Discontinuation of therapy with azithromycin and the
administration of specific treatment for C. difficile should be considered.
Streptococcal infections
Penicillin is usually the first choice for treatment of pharyngitis/tonsillitis due to Streptococcus pyogenes
and also for prophylaxis of acute rheumatic fever. Azithromycin is in general effective against
streptococcus in the oropharynx, but no data are available that demonstrate the efficacy of azithromycin
in preventing acute rheumatic fever.
Renal impairment
In patients with severe renal impairment (GFR < 10 ml/min) a 33% increase in systemic exposure to
azithromycin was observed (see section 5.2).
Myasthenia gravis
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).
Co-administration with hydroxychloroquine or chloroquine
Carefully consider the balance of benefits and risks before prescribing azithromycin for any
patients taking hydroxychloroquine or chloroquine, because of the potential for an increased risk
of cardiovascular events and cardiovascular mortality (see section 4.5).
Excipients
Lactose
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or
glucose- galactose malabsorption should not take this medicine.
Sodium
This medicine contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially
'sodium-free'.

Antacids: In a pharmacokinetic study investigating the effects of simultaneous administration of
antacids with azithromycin, no effect on overall bioavailability was seen, although peak serum
concentrations were reduced by approximately 24%. In patients receiving both azithromycin and
antacids, the drugs should not be taken simultaneously.
Cetirizine: In healthy volunteers, coadministration of a 5-day regimen of azithromycin with 20 mg
cetirizine at steady- state resulted in no pharmacokinetic interaction and no significant changes in the
QT interval.
Didanosine (Dideoxyinosine): Coadministration 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: Concomitant administration of macrolide antibiotics, including azithromycin, with Pglycoprotein
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-glycoprotein substrates such as
digoxin are administered concomitantly, the possibility of elevated serum digoxin concentrations should
be considered. Clinical monitoring, and possibly serum digoxin levels, during treatment with azithromycin
and after its discontinuation are necessary.
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 drugs
known to undergo significant cytochrome P450 mediated metabolism.
Atorvastatin: Coadministration 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).
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.
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 dose of 15 mg warfarin administered to healthy volunteers. There
have been reports received in the post-marketing period of potentiated anticoagulation subsequent to
coadministration 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 Cmax and AUC0-5 were found to be significantly elevated (by 24%
and 21% respectively), however no significant changes were seen in AUC0-∞. Consequently, caution
should be exercised before considering concurrent administration of these drugs. If coadministration of
these drugs is necessary, ciclosporin levels should be monitored and the dose adjusted accordingly.
Efavirenz: Coadministration of a single dose of 600 mg azithromycin and 400 mg efavirenz daily for 7
days did not result in any clinically significant pharmacokinetic interactions.
Fluconazole: Coadministration 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

Cmax (18%) of azithromycin was observed.
Indinavir: Coadministration 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, coadministration 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: Coadministration 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 was required.
Rifabutin: Coadministration of azithromycin and rifabutin did not affect the serum concentrations of either
drug.
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 Cmax 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, coadministration 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: Coadministration 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.
Hydroxychloroquine and chloroquine: Azithromycin should be used with caution in patients receiving
medicines known to prolong the QT interval with potential to induce cardiac arrhythmia, e.g.
hydroxychloroquine. Observational data have shown that co-administration of azithromycin with
hydroxychloroquine in patients with rheumatoid arthritis is associated with an increased risk of
cardiovascular events and cardiovascular mortality. Carefully consider the balance of benefits and risks
before prescribing azithromycin for any patients taking hydroxychloroquine. Similar careful consideration
of the balance of benefits and risk should also be undertaken before prescribing azithromycin for any
patients taking chloroquine, because of the potential for a similar risk with chloroquine.

Pregnancy
There is a large amount of data from observational studies performed in several countries on exposure
to azithromycin during pregnancy, compared to no antibiotic use or use of another antibiotic during the
same period (>7,300 first trimester exposures). While most studies do not suggest an association with
adverse foetal effects such as major congenital malformations or cardiovascular malformations, there is
limited epidemiological evidence of an increased risk of miscarriage following azithromycin exposure in
early pregnancy.
Therefore, azithromycin should only be used during pregnancy if clinically needed and the benefit
of treatment is expected to outweigh any small increased risks which may exist.
Breast-feeding
Limited information available from published literature indicates that azithromycin is present in human
milk at an estimated highest median daily dose of 0.1 to 0.7 mg/kg/day. No serious adverse effects of
azithromycin on the breast- fed infants were observed.
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from
azithromycin therapy taking into account the benefit of breast-feeding for the child and the benefit of
therapy for the woman.

No data are available regarding the influence of azithromycin on a patient's ability to drive or operate
machinery.
However, the possibility of undesirable effects like dizziness and convulsions should be taken into
account when performing these activities.

Azithromycin is well tolerated with a low incidence of side effects.
The table below lists the adverse reactions identified through clinical trial experience and post-marketing
surveillance by system organ class and frequency. Adverse reactions identified from post-marketing
experience are included in italics. 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

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 to report any suspected adverse reactions via the National Pharmacovigilance Center (NPC) with contact
information :
To report any side effect(s)

National Pharmacovigilance Center (NPC)

o SFDA Call Center: 19999.
o E-mail: npc.drug@sfda.gov.sa
o Website: https://ade.sfda.gov.sa/

Adverse events experienced in higher than recommended doses were similar to those seen at normal
doses.
Symptoms
The typical symptoms of an overdose with macrolide antibiotics include reversible loss of hearing,
severe nausea, vomiting and diarrhoea.
Treatment
In the event of overdose, the administration of medicinal charcoal and general symptomatic treatment
and supportive measures are indicated as required.

General properties
Pharmacotherapeutic group: Antibacterials for systemic use, macrolides. ATC code: J01FA10.
Mode of action
Azithromycin is a macrolide antibiotic belonging to the azalide group.
The molecule is constructed by adding a nitrogen atom to the lactone ring of erythromycin A. The
chemical name of azithromycin is 9-deoxy-9a-aza-9a-methyl-9a-homoerythromycin A. The
molecular weight is 749.0.
Mechanism of action
The mechanism of action of azithromycin is based upon the suppression of bacterial protein
synthesis by means of binding to the ribosomal 50S sub-unit and inhibition of peptide translocation.
Mechanism of resistance:
o SFDA Call Center: 19999.
o E-mail: npc.drug@sfda.gov.sa
o Website: https://ade.sfda.gov.sa/
Resistance to azithromycin may be inherent or acquired. There are three main mechanisms of
resistance in bacteria: target site alteration, alteration in antibiotic transport and modification of the
antibiotic.
Azithromycin demonstrates cross resistance with erythromycin resistant gram positive isolates. A
decrease in macrolide susceptibility over time has been noted particularly in Streptococcus
pneumoniae and Staphylococcus aureus. Similarly, decreased susceptibility has been observed
among Streptococcus viridans and Streptococcus agalactiae (Group B) streptococcus against
other macrolides and lincosamides.
Breakpoints
Azithromycin susceptibility breakpoints for typical bacterial pathogens, as published by EUCAST are:

Susceptibility
The prevalence of acquired resistance may vary geographically and with time for selected species
and local information on resistance is desirable, particularly when treating severe infections. As
necessary, expert advice should be sought when the local prevalence of resistance is such that the
utility of the agent in at least some types of infections is questionable.

Paediatric population
• Following the assessment of studies conducted in children, the use of azithromycin is not
recommended for the treatment of malaria, neither as monotherapy nor combined with chloroquine
or artemisinin based drugs, as non- inferiority to anti-malarial drugs recommended in the treatment
of uncomplicated malaria was not established.

Absorption
Bioavailability of azithromycin after oral administration is approximately 37%. Peak plasma
concentrations are attained after 2-3 hours. The mean maximum concentration observed (Cmax) after
a single dose of 500 mg is approximately 0.4 μg/ml.
Distribution
Orally administered azithromycin is widely distributed throughout the body.
In pharmacokinetic studies it has been demonstrated that the concentrations of azithromycin
measured in tissues are noticeably higher (as much as 50 times) than those measured in plasma,
which indicates that the agent strongly binds to tissues. Binding to serum proteins varies according
to plasma concentration and ranges from 12% at 0.5 microgram/ml up to 52% at 0.05 microgram
azithromycin/ml serum. The mean volume of distribution at steady state (VVss) has been
calculated to be 31.1 l/kg.
At the recommended dose no accumulation appears in the serum. Accumulation appears in tissues
where levels are much higher than in serum. Three days after administration of 500 mg as a single
dose or in partial doses concentrations of 1,3-4,8 μg/g, 0,6-2,3 μg/g, 2,0-2,8 μg/g and 0-0,3 μg/ml
have been measured in resp. lung, prostate, tonsil and serum.
In animal tests, high concentrations of azithromycin have been found in phagocytes. It has also
been established that during active phagocytosis higher concentrations of azithromycin are
released from inactive phagocytes. In animal models this results in high concentrations of
azithromycin being delivered to the site of infection.
Elimination
The terminal plasma elimination half-life closely reflects the elimination half-life from tissues of 2-4
days.
Approximately 12% of an intravenously administered dose is excreted in unchanged form with the
urine over a period of 3 days; the major proportion in the first 24 hours. Concentrations of up to 237
μg/ml azithromycin, 2 days after a 5-day course of treatment, have been found in human bile. Ten
metabolites have been identified (formed by N- and
O-demethylation, by hydroxylation of the desosamine and aglycone rings, and by splitting of the
cladinose conjugate). Investigations suggest that the metabolites do not play a role in the
microbiological activity of azithromycin.
Pharmacokinetics in Special populations:
Renal Insufficiency
Following a single oral dose of azithromycin 1 g, mean Cmax and AUC0-120 increased by 5.1%
and 4.2% respectively, in subjects with mild to moderate renal impairment (glomerular filtration rate
of 10-80 ml/min) compared with normal renal function (GFR > 80ml/min). In subjects with severe
renal impairment, the mean Cmax and AUC0-120 increased 61% and 35% respectively compared
to normal.
Hepatic insufficiency
In patients with mild to moderate hepatic impairment, there is no evidence of a marked change
in serum pharmacokinetics of azithromycin compared to normal hepatic function. In these patients,
urinary recovery of azithromycin appears to increase perhaps to compensate for reduced hepatic
clearance.
Elderly
The pharmacokinetics of azithromycin in elderly men was similar to that of young adults; however,
in elderly women, although higher peak concentrations (increased by 30-50%) were observed, no
significant accumulation occurred.
In elderly volunteers (> 65 years) higher (29%) AUC values have been measured after a 5 day
treatment than in younger volunteers (< 45 years). These differences are not regarded as clinically
relevant; dose adjustment is therefore not recommended.
Infants, toddlers, children and adolescents
Pharmacokinetics has been studied in children aged 4 months – 15 years taking capsules,

granules or suspension. At 10 mg/kg on day 1 followed by 5 mg/kg on days 2-5, the Cmax
achieved is slightly lower than in adults, with 224 μg/l in children aged 0.6-5 years and after 3
days dosing, and 383 μg/l in those aged 6-15 years. The half-life of 36 h in the older children was
within the expected range for adults.

Phospholipidosis (intracellular phospholipid accumulation) has been observed in several tissues
(e.g. eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) of mice, rats, and
dogs given multiple doses of azithromycin. Phospholipidosis has been observed to a similar extent
in the tissues of neonatal rats and dogs. The effect has been shown to be reversible after
cessation of azithromycin treatment. The relevance of this finding to humans receiving
azithromycin in accordance with the recommendations is unknown.
Electrophysiological investigations have shown that azithromycin prolongs the QT interval.
Carcinogenic potential:
Long-term studies in animals have not been performed to evaluate carcinogenic potential as the
drug is indicated for short-term treatment only and there were no signs indicative of carcinogenic
activity.
Mutagenic potential:
There was no evidence of a potential for genetic and chromosome mutations in in-vivo and in-vitro
test models.
Reproductive toxicity:
In animal studies for embryotoxic effects of the substance, no teratogenic effect was observed in
mice and rats. In rats, azithromycin doses of 100 and 200 mg/kg bodyweight/day led to mild
retardation of foetal ossification and in maternal weight gain. In peri- and postnatal studies in rats,
mild retardation following treatment with 50 mg/kg/day azithromycin and above was observed.

Core: Pre-gelatinized starch dry, Dicalcium phosphate anhydrous, Crospovidone NF, Klucel EF, Colloidal
silicon dioxide, Stearic acid B.P.C., Magnesium stearate, Sodium lauryl sulphate.
Coating Materials: Polysorbate 80, Titanium dioxide pharm grade, Purified talc, Polyethylene glycol MW
6000, Hydroxypropyl methylcellulose.

Not applicable.

Store below 30 oC.

White opaque PVC/PVDC reel blister strips with hard tempered aluminium foil lid.

blister with 2, 3, 4, 6 and 12 film-coated tablets.
Not all pack sizes may be marketed.

Not applicable.