Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic that is highly effective against both gram-positive and gram-negative bacteria. It was the first quinolone developed that could be administered orally to treat serious infections. A new extended release formulation, CiproMega, was developed to provide the benefits of once daily dosing for improved patient compliance compared to the previous twice daily dosing. Clinical trials demonstrated CiproMega was as effective as, and in some cases more effective than, the previous twice daily dosing regimen with fewer side effects.

1. 2012
Cipro Mega 1000 MG XL
Extended Release Tab
• Product Knowledge
By:
Dr. Mohammad Salah
Product Manager

2. 2012
CIPROFLOXACIN: A SUCCESS STORY
Ciprofloxacin, has become a remarkable success
story in the pharmaceutical industry, not only for
being the first oral antimicrobial drug with broad
spectrum that can be used to treat day-today as
well as serious infections, but also for its
penetration into the most common M.O.

3. 2012
a most potent vs. Pseudomonas
b more potent vs. S. pneumoniae and anaerobes than earlier compounds
c most potent vs. S. pneumoniae and anaerobes
Drugs 1999;58 Suppl 2:1-5
Quinolones: Classification
First Generation Nalidixic acid
Oxolonic acid
Cinoxacin
Second Generation Ciprofloxacina
Norfloxacin
Lomefloxacin
Ofloxacin
Levofloxacin
Third Generationb
Sparfloxacin
Gatifloxacin
Grepafloxacin
Fourth Generationc
Trovafloxacin
Moxifloxacin
Gemifloxacin

4. 2012
Ciprofloxacin: Chemical Structure
Ciprofloxacin is a 4-quinolone antibacterial drug
Ref : Drugs 1988 (35: 373-447)
F
O
CO2H
N
N
HN
Effective against gram-
positive and gram-
negative pathogens.
Effective against
pseudomonas
Confers potent
antimicrobial activity
Ciprofloxacin

5. 2012
CIPROFLOXACIN: ANTIBACTERIAL SPECTRUM
Antibacterial spectrum ciprofloxacin has in vitro activity against a wide range of gram-
negative, gram-positive and atypical pathogens.
Gram-positive Gram-negative Atypical
S.epidermidis E.coli, L.pneumophila
S.pneumoniae H.influenzae M.pneumoniae
S.pyogenes K.pneumoniae C.trachomatis
N.gonorrhoeae
P.mirabilis
S.typhii
Serratia,
Shigella
M.catarrhalis
Pseudomonas
Others: Mycobacterium tuberculosis

6. 2012
Mode of action
• Bactericidal
• Selectively inhibit DNA synthesis by acting on DNA
gyrase enzyme
• Extended spectrum covers almost all G-ve M.o and
G+ M.O also covers some atypical MO
• The most active quinolone against P.aeruginosa

7. 2012
Pharmacokinetics
• Absorption :ciprofloxacin is rapidly and well
absorbed after oral administration.
• Oral bioavailability 70%
• T Max 1-2 Hr
• Protein binding :30%
• Half life 3-5 hr

8. 2012
Pharmacokinetics
• Distribution :ciprofloxacin is widely distributed
throughout the body and concentrated in bile,
kidney ,gal bladder, liver, lung, pelvic organs and
prostate
With a concentration significantly higher than the MIC
of common pathogens.
• Metabolism
Only 10-20% is metabolized into 4 active forms.

9. 2012
Pharmacokinetics
• Excretion:
60-70% by kidney &the reminder by liver&intestinal mucosa.
Impaired renal function :
Creatinine clearance :
More than 20ml/min no dose adjustment
Less than 20 ml/min dose is decreased by half
No addional dosing changes for haemodialysis

10. 2012
Drug-Drug Interactions
• Antacids Divalent and trivalent cations
• Omeprazole inhibit absorption
• Theophylline inhibition of metabolism
• Cyclosporine
• Warafarin

11. 2012
Side effects
Articular damage
• Arthopathy including articular cartilage damage arthralgias
and joint swelling
• Observed in toxicology studies in immature dogs
• Led to contraindication in pediatric patients and pregnant or
breatfeeding women
• Risk vs benefits
• Tendon rupture dysglycemias and hypersensitivity

12. 2012
Side effects
Gastrointestinal 5%
• Nausea ,vomiting ,diarrhea and dyspepsia
Central nervous system
• Headech, agitation, insomnia, dizziness, rarely
hallucination and seizures
Hepato toxicity
• LFT elevation (led to withdrawal of trovafloxacin)
Photo toxicity

13. 2012
MEGA ERA
Cipro Mega1 gm XL
Ciprofloxacin 1000 mg

14. 2012
Cipromega 1gm XL
• XL ciprofloxacin was a big
challenge because of a very
narrow absorption window of
ciprofloxacin.
• Ciprofloxacin gets absorbed
only from the stomach and
the duodenum which is
20-30 cms long.

15. 2012
•New formulation
• Tablets are formulated to release drug at a slower
rate compared to immediate-release tablets.
Approximately 35% of the dose is contained within
an immediate-release component, while the
remaining 65% is contained in a slow-release matrix.

16. 2012
Cipromega OD diffuses
Ciprofloxacin gets
dissolved in acidic
medium, diffusing out in
a controlled manner.

17. 2012
Comparison between cipromega and
ciprofloxacin twice
CiproMega 1 gm xl Ciprofloxacin 5oo BID
Absorption 1-4 hr 1-2
Distribution 20-40 protein binding 20-40 protein binding
Metabolism Four metabolites Four metabolites
Elimination approximately 35% of an orally
administered dose was
excreted in the urine as
unchanged drug
approximately 35% of an orally
administered dose was
excreted in the urine as
unchanged drug

18. 2012
Cmax
(mg/L)
T1/2 (hr) Tmax (hr)§
CIPRO XR 1000 mg QD 3.11 ± 1.08 6.31 ± 0.72 2 (1-4)
CIPRO 500 mg BID 2.06 ± 0.41 5.66 ± 0.89 2 (0.5-3.5)
§ median (range)

19. 2012
Concentration dependent
Dose (mg)
Maximum
Serum
Concentrations
(mcg/mL)
Area
Under Curve
(AUC)
(mcg•hr/mL)
250
500
750
1000
1.2
2.4
4.3
5.4
4.8
11.6
20.2
30.8

20. 2012
Double peak serum concentration

21. 2012
CIPROMEGA Distribution
Intestinal mucosa concentration > 3times serum concentration
Bile concentration >6 times serum concentration
Intracellular concentration 3-6 times extracellular
concentration
APR Wilson; ciprofloxacin 10 years of clinical experience 1997.

22. 2012
CiproMega XL:
Mega proven efficacy vs. twice daily dose ciprofloxacin
a randomized, double-blind, controlled clinical trial conducted in the US and Canada.
The study enrolled 1,042 patients (521 patients per treatment arm) and compared CIPRO XR
)1000mg once daily for 7 to 14 days(
with immediate-release ciprofloxacin (500 mg BID for 7 to 14 days(.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard - Tenth Edition. CLSI Document M2-A10, Vol. 29, No. 1, CLSI, Wayne, PA, January, 2009.

23. 2012
Demonstrates Rapid Symptom Improvement
and Early Return to Activities in Patients
Suffering
From Uncomplicated Urinary Tract Infections
Patients Report First Signs of Symptom Relief in Just Three Hours
A total of 264 adult female outpatients with acute uncomplicated UTIs were
Enrolled in an open label, non-controlled, phase IV study conducted in 28
health centers in the United States. Female patients answered serial
questionnaires to track time to symptom relief, and received once-daily
extended-release ciprofloxacin 500 mg tablets for 3 days.
Colgan R.Survey of symptom burden in women with uncomplicated urinary tract infections.Clin Drug Invest. 2004; 24(1):55-60

24. 2012
Complicated Urinary Tract Infections and Acute
Uncomplicated Pyelonephritis
CIPRO Mega
1000 mgQD
CIPRO
500 mg BID
Randomized Patients 521 521
Per Protocol Patients^ 206 229
Bacteriologic Eradication at TOC
(n/N)*
148/166 (89.2%) 144/177 (81.4%)
CI [-0.7%, 16.3%]
Bacteriologic Eradication (by organism) at TOC (n/N)**
E. coli 91/94 (96.8%) 90/92 (97.8%)
K. pneumoniae 20/21 (95.2%) 19/23 (82.6%)
E. faecalis 17/17 (100%) 14/21 (66.7%)
P. mirabilis 11/12 (91.6%) 10/10 (100%)
P. aemginosa 3/3 (100%) 3/3 (100%)
Clinical Cure at TOC (n/N)*** 159/166 (95.8%) 161/177 (91.0%)
CI [-1.1%, 10.8%]
AUP Patients
Bacteriologic Eradication at TOC
(n/N)*
35/40 (87.5%) 51/52 (98.1%)
CI [-34.8%, 6.2%]
Bacteriologic Eradication of E.
coli at TOC (n/N)**
35/36 (97.2%) 41/41 (100%)

25. 2012
Urinary Bactericidal Activity of Extended-Release Ciprofloxacin (1,000
Milligrams) versus Levofloxacin (500 Milligrams)
Strain MIC Cipro
1000mg
MIC Levo500mg
E. coli
K. pneumoniae 595
0.008
0.125
0.03
0.25
P. mirabilis
P. aeruginosa
S. aureus
S. saprophyticus
E. faecalis
0.03
0.5
0.125
0.25
1
0.06
2
0.125
0.25
1

26. 2012
cipromegaXL Highlights: Antimicrobial Spectrum
• Most active of the quinolones against Pseudomonas.
• More active than ofloxacin against Moraxella catarrhalis
and Chlamydia trachomatis.
• Greater or similar activity against Neisseria spp. than
Cefotaxime or Ceftazidime.
• S. typhi resistant strains are susceptible to ciprofloxacin
1) Clinical Therapeutics 21(1) 1999:3-40
2) Ciprofloxacin, 10 years of Clinical Experience by Wilson et al.

27. 2012
Resistance To CIPROFLOXACIN
• In a survey of 67,000 isolates in the USA, most enterobacteriaceae
(99%), Staphylococci (98%) and Pseudomonas aeruginosa (97%) were
still susceptible to ciprofloxacin
• On the basis of 1997-1999 test results of the SENTRY antimicrobial
surviellance results ,ciprofloxacin inhibited 100% of H. influenzae and
M. catarrhalis strains
Clinical infectious diseases 2000;31(suupl2):s16-s23
Ciprofloxacin : 10 years of clinical experience by wilson and Gruneberg

28. 2012
Why Cipro Mega once a day?
To enhance
patient
compliance

29. 2012
HIGHLIGHTS OF
Cipromega(CIPROFLOXACIN)
• The most potent fluorinated quinolone
• Has a very broad spectrum of antibacterial activity
• Ensures rapid bactericidal activity at very low concentrations
• Is rapidly distributed and adequate levels are achieved in most
tissues and body fluids with high intracellular concentrations in
the phagocytes
• Good bioavailability with an extended half-life of elimination

30. 2012
HIGHLIGHTS OF
Cipromega(CIPROFLOXACIN)
• AUC/MIC ratios against various pathogens > 100
• Cmax/MIC ratios are in excess of 8-12
• Has proven efficacy in many types of systemic infections as well as
both chronic and acute infections
• Available as tablets
• Convenient once-daily dosage
• Well tolerated by all patients

31. 2012
Cipromega-xl: Skin and skin structure infections
No of patients
27
Treatment
Cipromega 1000 mg tablet once daily for 10 days.
Clinical cure or improvement 96%
Bacteriological Eradication 90.5%
(Organisms eradicated:S.aureus,S.pyogenes,klebsiella)
Safety
No serious adverse events reported
Conclusion
Cipromega -OD tablets are highly effective and safe in the treatment of skin and skin
structure infections.
Ref.: Data on file

32. 2012
Cipromega-OD :- Uncomplicated Urinary Tract
Infection
No of patients
24
Treatment
Patients received treatment with cipromega 500mg tablet once a day or
conventional release ciprofloxacin 250mg tablet twice a day for 3 days.
Outcome Ciprofloxacin Ciprofloxacin
500mg OD 250mg bid
(n=12) (n=12)
Clinical cure 100 % 91.7 %
Bacterial Eradication(E.coli,
Klebsiella,Pseudomonas) 100 % 85 %
Safety
No adverse events were reported.
Ref : data on file.

33. 2012
Cipromega-OD : Safety and Tolerability
• Cipromega-OD (as 500 mg od or 1000 mg od) is safe
and well tolerated
• Adverse effects (Nausea, gastritis) were 4.3% similar
with that observed with conventional tablet
• No discontinuation of therapy observed with cipromega
-OD
Data on file

34. 2012
Cipromega -OD: Indications
Cipromega -OD is indicated for the treatment of the following
infections caused by susceptible microorganisms.
• Acute sinusitis
• Lower respiratory infections including pneumonia and acute
exacerbations of chronic bronchitis.
• Chronic bacterial prostatitis
• Complicated intra-abdominal infections (used in combination with
metronidazole)
• Skin and skin structure infections
• Bone and joint infections
• Infectious diarrhoea
• Typhoid fever

35. 2012
Cipromega -OD: Dosage and administration
Directions for use of cipromega-OD 500 mg and cipromega-OD 1000 mg tablets:
Infections Type of Severity Daily Dose Frequency Usual
of adminis- Duration †
tration of OD
Acute Moderate 1000 mg q 24 h 10 days
Sinusitis
Lower Mild/Moderate 1000 mg q 24 h 7 -14 days
Respiratory Severe/ 1000 mg q 24 h 7 -14 days
Tract Complicated

36. 2012
Cipromega-OD: Dosage and administration
(Contd.)
Infections Type of Severity Daily Dose Frequency Usual
of adminis- Duration †
tration of OD
Urinary Tract Acute 500 mg q 24 h 3 days
Uncomplicated
Mild/Moderate 500 mg q 24 h 7 -14 days
Severe/Compli- 1000 mg q 24 h 7 -14 days
cated
Chronic Bacte- Mild/Moderate 1000 mg q 24 h 28 days
rial Prostatitis
Intra-abdominal* Complicated 1000 mg q 24 h 7 -14 days
Skin and skin Mild/Moderate 1000 mg q 24 h 7 -14 days
structure Severe/Compli- 1500 mg q 24 h 7 -14 days

37. 2012
Cipromega-OD: Dosage and administration (Contd.)
Infections Type of Severity Daily Dose Frequency Usual
of adminis- Duration †
tration of OD
Bone and joint Mild/Moderate 1000 mg q 24 h > 4 - 6
Infectious Severe/Complicated 1500 mg q 24 h > 4 - 6 weeks
diarrhoea Mild/Moderate/ 1000 mg q 24 h 5 -7 days
Typhoid fever severe
Mild/Moderate 1000 mg q 24 h 10 days
* used in conjunction with metronidazole
† generally ciprofloxacin should be continued for at least 2 days after the signs and
symptoms of infection have disappeared

38. 2012
Cipromega -OD Highlights
• Novel once daily formulation .
• AUC/MIC ratios and Cmax/MIC ratios higher for various organisms.
Thereby exhibits excellent bacterial power
• More bactericidal then conventional ciprofloxacin tablet
• Excellent efficacy in respiratory tract, skin and skin structure and
urinary tract infections
• Safe and well tolerated
• Enhance patient compliance

39. 2012
Cipromega
• URO
• SG
• I.M
• G.P
• Chest
• E.N.T

40. 2012
Competitores
Ofloxacin 200
Product company pack price
ofloxacin Sedico 10 Tab 25
Tarivid Aventis 10 Tab 47
Tarivan Alex 10 Tab 25
ofloxin Kahira 10 Tab 18

41. 2012
Levofloxacin250,500
Product company pack price
Tavanic Aventis 5 Tab 50-85
Levanic MUP 5 Tab 35
venexan sedico 5 Tab 25
Unibiotic Hipharm 5 Tab 25-37
Levoxin Amoun 5 Tab 25-50

42. 2012
Levofloxacin
• Efficacy
-UTI Same results with high rate of relapse
-RTI Better converge on H-influnza
-Skin&STI Better on pseudomonas
• Relapse rate
6.5%vs 13% in same indication
• Both are FDA approved and no liver effect

43. 2012
Cipro Mega Competitors
Product company pack price
Serviflox Sandoz 10 Tab 15-28-39
Cibrobay Bayer 10 Tab 26-46-65
Ciprofar Pharco 10 Tab 15-20-25
Ciprocin
EPICO
10 Tab 18-32-35
Cipromax Spemaco 10 tab 17-33
Rancif Ranbaxy 10 Tab 15-22.5
Ciprofloxacin America 10 Tab 16-30
Bactiflox Mepha 10 Tab 16-31
Ciproxil El rwad 5 tab 20

44. 2012
Other competitors
Product company pack price
Sparcin EMA 10 Tab 50
Avalox Bayer 5 Tab 90
Epinor EPICO 14 Tab 18
conaz Wock 10 Tab 15

45. 2012
SWOT analysis
STRENGTHS WEAKNESSES
- 10 tablets on one strip
- decrease area of penetration
- Poor management
- Very long molecule development
time
- Poor brand awareness
- Unreliable customer service
OPPORTUNITIES
- Emerging markets
- Growing demand
- Changing customer needs
- New product uses
- New regulations
- New distribution channels
THREATS
- New competitor with more
technology
- Potential resistance to molecule
- New regulations
- Declining population
- Market saturation

46. 2012
Campaign strategy
•To build the concept of once daily dose mega ERA penetration
in UTI for complicated and uncomplicated UTI.
• Differentiation between Cipromega once daily
and other ciprofloxacin twice daily
Penetrate Urologists and surgeons clinics

47. 2012
Tactics:
•Regular visits with Urologists with good interval time
between each visit .
•Aggressive promotion to increase awareness of once daily dose
with AM centers
•Penetrate to reach to the customer
•Promotion mix to increase relation with our main specialty.

48. 2012
AM Activity
1-General & Educational Hospitals first priority:
Urology Department
SGs Department
IM Department
2-Tropical Hospitals
3-Rual Units

49. 2012
Action plan
•Preparation of binder with highly powerful studies.
•Using 15 groups meeting allover the country.
•3 major stand alone meeting supporting once daily efficacy.
•Highly microbiology and product knowledge that power our MR
•Sponsor for 50 customers by the end of the year2012.
•Sponsor in 3 major conferences 2 UR and one SGs
•Unlimited A.V actions at least 15 Av Action per Area
•Sponsor for SGs club meeting in each area
•Monthly meeting per territory to update and brain storm.
•Using sampling and valuable gifts differentiate us from
Competitores.

50. 2012
Time plan
Promotion mix
Jan Feb Mar Apr May Jun Jul Aug Sept Oct Nov Dec
Printing Material B.N√
L.B√ L.B√ B.N√
Gimmicks
Cloves-Makentosh √ √ √
Gifts
Surgical dre- √ √
A.V actions(200) √ √ √ √ √ √ √ √ √ √ √ √
Special gifts(200) √ √
3 Stand alone meeting √ √ √ √
Group meeting √ √ √ √ √ √ √ √ √ √ √ √

51. 2012
Targeted customer:( PM Activity)
•Urologists
•SGs
•IM
Gps

52. 2012
Serviflox
15%
Ciprofar
38%
Ciprocin
21%
Ciproxil
3%Cipro
23% Serviflox
Ciprofar
Ciprocin
Cipro
Ciproxil
Ciprofoxacin market sales 2011

53. 2012
Sales overview 2011
586,774
2,002,976
1,087,167
856,145
164000
0
500,000
1,000,000
1,500,000
2,000,000
2,500,000
Serviflox Ciprofar Ciprocin Cipro Ciproxil
Units

54. 2012
Market Growth
10
12
15
33
50
0
10
20
30
40
50
Serviflox Ciprofar Ciprocin Cipro Ciproxil
GR%

55. 2012

56. 2012
First visit once daily
• Cipromega 1gm XL once daily
• Mega ERA and superiority over
levofloxacin in complicated UTIs
• Mega choice and Mega Efficacy.
• Mega Rapidity and Mega safety over
twice daily .

57. 2012
Second visit
• Cipromega 1gm XL once daily
• Mega ERA
• Mega Efficacy and Mega maintenance.
• Mega Rapidity and Mega cure
• Mega prophylaxis
• Mega safety and Mega Tolerability

58. 2012