Zi-Once

Mohamed Elhoseny
Regional Product Manager Gulf

For Internal Use Only

AZI-ONCE
TRAINING MODULE

2
 “While
you teach,
you learn.”
 Win – Win Transaction
My expectations fro Your expectations f
My objectives Your Objectives
m you rom me

-To pass knowledge -To be attentive -To pass knowledge -To gain knowledge
-To pass experience -To probe
-To pass experience -To gain experience
-To facilitate -To seek guidance
applications -To participate -To guide -To be able to apply
-To learn -To keep in touch -To be nice -To have fun
-To gain new -To give good .
friends
marks.
Important questions to answer routinely before selecting
an antibiotic

1. Is an antibiotic indicated?
2. Have appropriate specimens been obtained, examined, an
d cultured?
3. What organisms are most likely?
4. If several antibiotics are available, which is best? (This que
stion involves such factors as drugs of choice, pharmacok
inetics, toxicology, cost, narrowness of spectrum)
5. Is an antibiotic combination appropriate?
6. What are the important host factors?

7. What is the best route of administration?

8. What is the appropriate dose?

9. Will initial therapy require modification after culture data ar

e returned?

10.What is the optimal duration of treatment, and is developm

ent of resistance during prolonged therapy likely to occur?

Reese and Betts. A Practical Approach to Infectious Diseases Fourth edition, 1993.
 Macrolides
Macrolides were discovered in 1952,
beginning with erythromycin, then Spi
ramycin, Roxithromycin and recently
Clarithromycin and Azithromycin (Azi
-Once).
 Macrolides Classification

14-membered ring 15-membered ring 16-membered ring

Natural co Semi-synthetic Spiramycin (Rovamy

mpound derivatives Azalides cin)
Josamycin (New)
Rokitamycin (New)
Erythromycin

Roxithromycin (R
Azi-Once
ulid)
Clarithromycin (Kl
acid)
 Azalides (Azi-Once)
Chemically Azi-Once has a methy
l substituted nitrogen atom at posi
tion 9a in the lactone ring of Eryth
romycin.
Macroides
 Microbiology
Mode of Action:
Azi-Once acts by interfering with bacterial
ribosomal function.
It inhibits bacterial polypeptide synthesis by
binding to the 50s ribosomal submit and pr
eventing translocation of peptides.
 Azi-Once advantages over Macrolides
Azi-Once novality in mechanism of action provides
higher concentration inside phagocyte cells is abou
t 200-600 times than the serum.

No drug-drug interaction have been reported with

Azi-Once (Terfenadine, Theophyllins, Warfarin, etc.
.), while Erythromycin & Clarithromycin have.
Azi-Once advantages over Macrolides

Azi-Once dose is both simple and convenient to

the patient and the physician ensuring the best
clinical and bacteriological success.

Just with 3 once daily doses you acquire a full

course of treatment.
1. Infection
2. Inflammation
3. Chemotactic Agents
4. Phagocytes (+ Azi-Once)
5. Azi-Once is released at the sight of in
fected during phagocytosis.
 The presence of intracellular Azi-Onc
e within phagocytes, may be associat
ed with enhanced synergistic activity
with the host immune system.
 Pharmacokinetics
Absorption and distribution:-
– Rapid distribution & Sustained high tissues conc.
– half-life of 68 hours (3 days).
– Good acid stability.

– Good oral bioavailability 37%.

– protein binding (7%)

– Uptake and transport by phagocyte cells to the site of infection.

– Mainly excreted through bile.

 Pharmacokinetics
In contrast to the comparatively low levels o
f Azi-Once seen in serum and plasma, Azi-
Once reaches significantly higher concentra
tion in a wide range of tissues to reach up t
o 200-600 times its serum concentration or
even more.
 Azi-Once
Gram Positive Aerob Gram Negative Aerob Anaerobic Bacteria Other Organisms
es es
- Staphylococcus aur -Bordetella pertussis -Bacteroides bivius - Borrelia burgdorferi
eus - Campylobacter jejun - Clostridium perfring -- Chlamydia trachom
- Streptococcus spp ( i ens atis
groups C,F, G and viri - Haemophilus ducreyi - Peptostreptococcus s - Mycoplasma pneum
dans) - Haemophilus influen pp oniae
- Streptococcus agal zae - Prevotella bivia - Mycoplasma homini
actiae -Legionella pneumop s
- Streptococcus pneu hila -- Treponema pallidu
moniae -Moraxella catarrhalis m
- Streptococcus pyog -Ureaplasma urealytic
-Neisseria gonorrhoea
enes e um
- Mycobacterium aviu
m
-- Mycobacterium intr
acellulare
-Legionella pneumop
hila
29
 Azi-Once concentration in different body tissues an
d fluids after a single 500 mg oral dose.

TISSUE Azi-Once conc.(Mcg) after 500mg

single dose.
Sinus mucosa (chronic sinusitis) 4.01
Tonsillar tissue 4.5
Pulmonary tissue 3.94
Prostatic tissue 2.54
Various gynecological tissue 1.44
Gastric tissue 4.61
 Azi-Once Conc. in Tonsils & Lung 1,2

Tonsil
10.3 7.2 9.3
10

3.9 1.5
3.4 Lung 3.3
2.9 2.8
1 S. pyogenes MIC 90
H. influenzae MIC90

0.
1
S. pneumoniae MIC 90
M. catarrhalis MIC 90

0.01 Time (days)

0 1 2 3 4 5 6 7 8 9 10 11
Ref : 1- Vaudaux BP. J Antimicrob Chemother 1996 2- Cazzola M. Int J Clin Pharmacol Ther 1994
In recent studies, following administration of a single
500mg oral dose to patients under bronchoscopy

Azi-Once was found in:

Sputum.
Bronchial mucosa.
Tonsillar tissue.
Middle ear tissue fluid.
Epithelial lining fluid.
Alveolar macrophages.
with a very high concentration for up to 96 hours after
this single dose.
 Azi-Once Spectrum

Coverage of main causative microorganisms including:

Gm +ve (Streptococcus pneumoniae, Strept.Pyogens & Staph. aureus) .

Gm -ve (H. Influenzae, Moraxella catarrhalis)

Atypical pathogens (Legionella pneumophila, Mycoplasma pneumoniae &

Chlamydia spp).

Anaerobes (peptococcus, peptostreptococcus, clostridium perfringens & B

acteriodes fragilis.
In-vitro susceptibility of Gm-ve bacteria:
One of the major advantages of Azi-Once over :
• Other Macrolides..
• 1st generation Cephalosporins.
Is its superiority in the in-vitro potency against G
m-ve organism, especially H.Influenzae and M
oraxella catarrhalis.
In-vitro susceptibility of Enterobacteriaceae:
• E-coli.

• Salmonella.

• Shigella.
In-vitro bactericidal activity:
• Azi-Once produces prolonged high tissue c
onc. At the site of infection, consistently ab
ove the MIC for several days.
• Azi-Once have a bactericidal action in clin
ical practice.
• Azi-Once bactericidal effect is very rapid (i
t kills 99.9% of H. Influenzae within 4-6 hou
rs), while other macrolides need more than
24 hours to give the same effect.
Main approved indications for Azi-Onc
e are:
1. Upper respiratory tract infections.
2. Lower respiratory tract infections.
3. Skin & soft tissue infections.
4. Sexually transmitted diseases
Upper Respiratory Tract infection
s
Mainly Includes :
 Acute bacterial Pharyngitis/Tonsillitis
 Otitis media
 Sinusitis
 Duration of antibiotic treatment in URTIs

 Pharyngitis / Tonsillitis
- According to the International guidelines it should be treated f

or 10 days (1)
- Complete bacterial eradication is an important factor in preve
nting complications.

 Otitis Media

 Antibiotic treatment should be maintained for 10 days (2).

1)Nelson, 16th edition, 2000
2) Group A Streptococcal infections, NIAID Fact Sheet, National Institute of Allergy and
infectious diseases, 1999.
 Tonsillitis /Pharyngitis M.O.

1. Streptococcus pnemoniae.
2. Streptococuss pyogens (spe. GABHS).
3. H. Influenzea.
4. Maroxella catarahlis
 Lymphadenitis

Lymphadenitis is the inflammation and/or enlargement of a lymph node. Lymph node e

nlargement is common in children. Most cases represent a response to benign, local, or
generalized infections (usually viral). Lymphadenitis may affect a single node or a locali
zed group of nodes (regional adenopathy) and may be unilateral or bilateral. The onset
and course of lymphadenitis may be acute, subacute, or chronic.1
 Bone: Mastoid portion of the temporal bone

Mastoiditis is an infection of mastoid process, the portion of the temporal bone of the s
kull that is behind the ear which contains open, air-containing spaces.[1][2] It is usually
caused by untreated acute otitis media (middle ear infection) and used to be a leading c
ause of child mortality. With the development of antibiotics, however, mastoiditis has be
come quite rare in developed countries. It is treated with medications and/or surgery.[1]
If untreated, the infection can spread to surrounding structures, including the brain, cau
sing serious complication
 GABHS Tonsillopharyngitis
School age disease
1.4
Cases per child-year

1.2

0.8

0.6

0.4

0.2

0
1 3 5 7 9 11 13 15
Age (years)
Steinhoff MC, Rimoin AW, Streptococcal Pharyingitis, 2004
 Azi-Once 20 mg Power

Azi-Once
Azi-Once

Azi-Once eradtication was 5 times greater than other comparetors

( aug, klacid, ceclor ect.. )
Guidelines on Management of ac
ute streptococcal pharyngitis
According to:
American Heart association (AHA).
American academy of pediatrics (AAP).
Infectious Diseases Society of America (IDSA
).
American Academy of Physicians Assistants.
(AAPA)
They Recommend Azi-Once 20mg/kg/day for
treatment of streptococal pharyngitis as it pr
ovides the best rate of GABHS eradication.
Double dummy is a technique for retaining the blind when administeri
ng supplies in a clinical trial, when the two treatments cannot be made
identical. Supplies are prepared for Treatment A (active and indistingu
ishable placebo) and for Treatment B (active and indistinguishable pla
cebo). Subjects then take two sets of treatment; either A (active) and
B (placebo).
Possible pathogens

Sinusitis

1. Streptococcus pneumonia
2. Haemophilus influenzae
3. Moraxella catarrhalis.

Infectious Diseases Society of America. Clin Infect Dis. 2007;44:S27-72.

Lower Respiratory Tract Infections

Mainly includes:
 Acute bronchitis
 Community-acquired pneumonia
 Acute exacerbation of chronic obstructive
pulmonary disease (COPD).
 Atypical pneumonia
Community-Acquired Pneumonia

Most Common Pathogens

Streptococcus pneumoniae.
Haemophilus influenzae.
Mycoplasma pneumoniae.
Chlamydia pneumoniae.
Mandell LA, Wunderink RG, Anzueto A, et al. Practice guidelines for th
e management of community-acquired pneumonia in adults. Infectio
us Diseases Society of America. Clin Infect Dis. 2007;44:S27-72.
ATS/IDSA 07
 Azi-Once dose
Dosage Frequency Duration
Children * 20 mg/ kg/ day Once daily (with n
In tonsillopharyngitis o regard to meals) 3 days
Adults+ 500 mg (2 x 250 mg)/ da Once daily (1
y hour before meal) 3 days

– +4 cap (1 gm) single shot in STDs

*An alternative dose, given over 5 days with a single daily dose of 10 mg / kg on day 1, than 5 mg / kg on
days 2-5 .
In streptococcal pharyngitis/tonsillitis, similar clinical efficacy was observed at dose 10mg/kg or 2
0mg/kg for 3 days, however, greater bacteriological eradication was evident at the 20 mg/kg/day do
se.
 Azi-Once Safety
Clinical studies involving 4000 patients
Across a range of age (including children)
Data had shown Azi-Once to be well tolerated with a signific
antly lower incidence of adverse events compared to many s
tandard antibiotics
Of side effects reported with Azi-Once the vast majority were
classed as mild or moderate and included:
abdominal pain (2.5%)
diarrhea (3.6%)
nausea (2.6%)
 Azi-Once Safety

Rate of discontinuation due to side effects rep

orted to be:
– Azi-Once 0.2-0.7%
– Erythromycin 5.3% (30 times that of Azi-Once)
– B- lactam antibiotics 2.5% (10 times that of Azi-Once)

Pseudomembranous colitis ,was not reported

in any patients receiving Azi-Once
No drug-drug interaction has been reported w
ith many drugs including Theophylline, Terfen
adine Warfarin, Cimetidine, Carbamazepine,
and Methylprednisolone

Absence of neurological abnormalities

No dosage adjustment necessary in elderly p

atients or those with mild-moderate renal or h
epatic impairment
“ Summary of Azi-Once main benefits”

Azi-Once has worldwide proven recom

mendations with its simple dose.

About 400 Mns patients worldwide were

treated successfully with Azithromycin,
and up 1500 published clinical studies a
ll over the world.
Extended spectrum covering major G
m + ve, Gm -ve and atypical organism
s,

Unique activity against H. Influenzae v

ersus all macrolides.

Acid Stability

Good oral bioavailability

Low protein binding (7%)

Taste of the pediatric form .

Effective, Convenient, Simple and

Easy dose.
Pediatric form taken with no regards to
meals

No reported drug-drug interactions with

commonly used drugs

The only oral antibiotic covering compl

ete course of therapy (10 days) with ju
st one box (3 doses)
Azi-Once VS AMOXYCILLINS
The need for 10 days By ensuring that patients complete 10 day
s of therapy with the 3 doses of Azi-Once, the rate of recurrence
& complications will be minimum with a rapid cure rate which will
save for the patients a lot of direct & indirect costs. This makes
Azi-Once very economic for the patients.

While with amoxycillins, patients will be asked to buy 3 boxes to

complete the 10 days therapy which is very difficult & rare espec
ially after disappearance of the main symptoms, which will lead t
o many complications and economical factors

For amoxicillin's to reach the effectiveness and results of Azi-O

nce it should be given for 10 complete days TID.
Azi-Once VS QUINOLONES
Quinolones Azi-Once
Tavanic / Avalox
Coverage of Variable coverage for gm + ve esp. Cover all gm + ve bacteria e
Gm + ve bacteria Streptococcus spp. sp. Staph. & Strept.

For adults only Adults-Ped

Dosage forms

once for 7days Once daily for just 3 days. (

Just 3 doses)
Dose
 Azi-Once VS QUINOLONES

Quinolones Azi-Once
- Severe GIT
- Liver (disturbances in liver enzymes) Mild & transient GIT side
Side effects - Kidney (disturbances in serum urea & effects. Safe to be used in
creatinine) children.
- CNS (headache, fatigue, convulsions &
hallucinations)
- Contraindicated in children & old age with
history of cerebral strokes.
- Cartilage damage.

Drug
interaction Interact with theophylline, Caffeine, No drug- interaction.
antacids & probenecid.
N.B. Leading quinolones were Tarivid & Ciprofloxacillin.
 Azi-Once VS (2 ND GENERATION CEPHALOSPORINS)
( Cefzil, Ceclor, Zinnat)

Cefzil, Ceclor, Zinnat Azi-Once

B- Lactamase Stabilit It is better than 1st gene. Cephalos B- lactamase stable.

y porins, but lower than 3rd gene. &
Azi-Once.
Intracellular (atypical Doesn’t cover any of them Cover all intracellular bacteria esp.
bacteria) Mycoplasms & legionella.
Bid for 10 days (20 doses needed) Once daily for just 3 days (only 3 d
Dose
oses)

GIT side effects, allergy & hyperse Mild & transient GIT side effects w
Side effects
nsitivity. hich is not worse than 7%.

(N.B.) Zinnat Suspension main defect is its emetic very bad taste.
The same can be applied on Ceclor but its dose is from BID-TID and its taste is palatable.
Azi-Once VS 1st GENERATION CEPHALOSPORINS
1st GENE. CEPH Azi-Once
B-lactamase Stabil Not B- lactamase stable (doesn’t cov B-lactamase stable.
ity er H. infl., M. catarrhalis & staph. au
reus.
Intracellular (atypi Not covered covered
cal) bacteria.
Dose
TID or QID for 10 days (30-40 doses Once daily for just 3 days (only 3
needed) doses)
Cost
You need from 3-4 boxes to cover th Only one box is a full course of t
e full course of therapy. reatment.

Side effects
GIT side effects, kidney damage, alle Mild & transient GIT side effects
rgy & hypersensitivity in more than , not more than 7%.
12% of the patients.
(N.B.) Leading 1st. gene. Cephalosporins are Velosef, Duricef, Keflex & Ceporex.
 Sexually transmitted diseases

Chlamydial infections (Urethritis or Cervicitis).

Non-Ghonococcal Urethritis.

Chlamydial infections& gonorrhea are the most comm

on STDs.
Chlamydial infections are often asymptomatic (patient will n
ot seek treatment especially women).
 STDs
 If chlamydial infection is not treated right, it will resul
t to a serious complications (endometritis, acute sal
pingitis, ectopic pregnancy and obstructive infertility
in women and epididymitis in men).

 Up to 20-25% of cases of gonorrhea are mixed with

chlamydial infections (so you have to treat both as l
ong as you treat your patient empirically).
 STDs
 Traditional therapies administration is in multiple
doses over several days (7-14 days).

 Due to the unique pharmacokinetics of Azi-Once,

clinical studies have confirmed the efficacy of the
1 gm single-dose therapy of Azi-Once in treating
STDs.
Chlamydial Infections
Management of Patients Who Have
Cervicitis
 Gonococcal Infections

Gonorrhea is the second most common

ly reported bacterial STD.
Azi-Once Cap. Azi-Once Susp.
Defend ENT, GPs Rxs Take the lead of all oral
Penetrate Gyna. susp. Antibiotics
segment Capitalize the impact of
Highlight the role of Azi- 20mg/kg/day and the
Once in LRT” Atypical” power of recovery.
over Augmentin Demonstrate Azi-Once 3
Build the trust of Azi- different volumes.
Once in s as effective,
issue Conc.,
 The power of recovery

The power of Azi-Once 20mg/kg once daily for 3 days in eradication of GAB
HS

The power of simplicity and tolerability

 Azi-Once cap. Opportunities:
 Azi-Once is internationally recommended* in
 Pelvic Inflammatory Disease
 Gonoccocal and non gonoccocal urethritis
 Cervicitis
 Chlamydia genital infections
 STD ( gonorrhea)

 Once versus 7-10 days Quinolone treatment

*Centers for disease control 2006

 Azi-Once in STDs

Recommended first choice in Sexua

lly transmitted Diseases

 Urethritis and cervicitis based on all Internationa

l Guidelines
Urethritis and cervicitis due to Chlamydia tracho
matis or Neisseria gonorrhoeae.
 Azi-Once cap. Opportunities:
 Azi-Once is internationally recommended* in
 Pelvic Inflammatory Disease
 Gonoccocal and non gonoccocal urethritis
 Cervicitis
 Chlamydia genital infections
 STD ( gonorrhea)

 Once versus 7-10 days Quinolone treatment

*Centers for disease control 2006

Azi-Once Competitive message

Amoxicillin/Clavulonic Quinolone
Acid: Comparable results in ½
Unique mode of action time.
Tissue conc. Safety to below 18 years
Low resistance old and above 65 years
old.
Coverage toward GABHS
and atypical
short course therapy (3
days) cover 10 days
treatment.
Hepato-toxicity
 Target doctors and indications
GP, IM & Chest GP & ENT
Acute Bronchitis Tonsillitis
Asthmatic Bronchitis Pharyngitis

 Gyn.  Ped.
 Pelvic Inflammatory disease  URTs
 Chlamydial infections  CAP
 Targeting all Class A and B Doctors

Desired Frequency / Month / PSR

Specialty A (HH) B (HL)
1-Ped. 2 3

2-ENT 2 2

3-Chest 2 2

4-Surg. & Dent 1 1

(selected)

5-Gyna. ( selected ) 1

6-GP (Ped.) 2 2

7-GP (others) 1 1

8-IM 1 1
 Azi-Once Customer / Marketing Mix Guidance

HL CUSTOMERS HH CUSTOMERS
 Recommendation: 40-50% of FF time allocati  Recommendation: 35-40 % of FF time allocat
on ion
 Focus on achieving a high frequency call rate  Focus on achieving high coverage of this gro
H with this group up
 Target group for use of real experience (AB us  Target Customers for catch – up doses
e) to highlight strong outcomes data Target group from which to develop advocate
B
 Target customer group for invitation to speake
r / symposia events
s / speakers
A
Market Value

LL CUSTOMERS LH CUSTOMERS
 Recommendation: 0 % of FF time allocation  Recommendation: 15-20 % of FF time allocation
Focus on achieving high coverage of this group

D
L

L Brand Value H
THANK YOU