3. Cobel Darou Medical Department

4. Fluoro quinolones Synthetic, broad-spectrum antibiotics
Gram-positive, Gram-negative, “Atypicals”
Newer agents: anaerobes and mycobacteria
Inhibit DNA gyrase and/or topoisomerase IV
Concentration-dependent, bactericidal activity
Generally well tolerated, however significant toxicities have resulted in several products being withdrawn from the market
Pregnancy and breast feeding : category c

5. Classification of Fuoroquinolones

6. HISTORY
Nalidixic acid ,a byproduct of chloroquine synthesis was marketed during 1960s for oral treatment of urinary tract infection and is still available
Bearing a fluorine atom at position c-6 make it active against nalidixic acid resistant entro bacteriaceae .
Substitutions at the C6,C7 positions improved antibacterial activity and pharmacological properties .

8. DNA gyrase prevents the relaxation of super coiled DNA that is required for normal transcription and replication .
Topoisomerase IV probably do the separation of replicated chromosomal DNA in to the respective daughter cells during cell division

9. 1-DNA gyrase prevents the relaxation of positively supercoiled DNA that is required for normal transcription .
2-topoisomeraseIV probably interferes with separation of replicated chromosomal DNA in to respective daughter cells .

10. Fluoroquinolones Spectrum of Activity: Gram-positive
Strong* Moderate Weak
Levofloxacin Ciprofloxacin# Norfloxacin
Moxifloxacin Ofloxacin
Gemifloxacin
*These drugs are considered “respiratory” quinolones given there potent activity versus S. pneumoniae
#Ciprofloxacin may also be considered “strong” for S. aureus

11. Spectrum of Activity: Gram-negative
Norfloxacin
Moxifloxacin
Gemifloxacin
Ofloxacin
CiprofloxacinLevofloxacin
Weak
Moderate
Strong
*covers Pseudomonas aeuruginosa

12. Quinolones: other pathogens
“Atypical” coverage
Predictably active against Mycoplasma & Legionella
Newer agents (not ciprofloxacin) reliably inhibit chlamydia
Anaerobes (B. fragilis)
Moxifloxacin has improved activity
M. tuberculosis & atypical mycobacteria
Newer drugs (moxi, levo) have good activity

13. Fluoroquinolones: spectrum of activity
Entreobacteriaceae is a large family of gr- facaltative anerobic bacteria include harmless symbyonts and pathogens eg. salmonella , E.coli , yersinia , klebsiella,shigella

14. Broad spectrum of coverage

15. FQ Pharmacokinetics
Well absorbed from the GI tract allowing oral administration to most patients – including hospitalized patients
Mixed route of elimination, depending upon agent.
Levofloxacin most dependent upon renal elimination.
80% eliminated from urine

16. Levofloxacin pharmacokinetics
Release &Absorption: is rapidly &completely absorbed after oral administration.peak plasma concentration is usually attained 1 to 2 hours after oral dosing and bioavailability is 99%.
Administration with food prolongs the time to peak
concentration by approximately 1 hour and decreases the C
max by 14%following tablet administration.
Distribution :has widespread distribution in to the body tissues.the skin tissue biopsy to plasma AUC ratio is 2
long tissue concentration is generally 2 to 5 fold higher than
plasma concentration. Bone tissue concentration ratio is 2 . It
penetrates well in prostate tissue

17. Levofloxacin Pharmacokinetics
Pr. binding capacity :is 24% to 38% and is independent of the drug concentration.
Half life : is 6 to 8 hours.
Metabolism :levofloxacin is stable in plasma and urine and does not convert to it’s enantiomer D- ofloxacin. Less than 5% is metabolised in the liver and convert to inactive metabolites.
Elimination :87% is primarily excreted as unchanged drug in the urine within 48 hours. 5% is excreted in urine as metabolites and 4% in feces in 72 hours .

18. Levofloxacin: optimal bioavailability for sequential therapy

20. Indication & Use
Levofloxacin is a fluoroquinolone antibacterial indicated in adults (≥18 years of age) with infections caused by designated, susceptible bacteria : * Pneumonia: nosocomial and community acquired . * Acute bacterial sinusitis * Acute bacterial exacerbation of chronic bronchitis * Skin and skin structure infections: complicated and uncomplicated * Chronic bacterial prostatitis * Urinary tract infections: complicated and uncomplicated * Acute pyelonephritis * Inhalational anthrax, post-exposure
The only indication permitted in children , is inhalational anthrax .

21. Dosage and Administration Dosage in patients with normal renal function
*Due to methicillin susceptible staph . aureous including MDR strep pneumonia
** due to strep . pneumonia excluding MDR isolates

22. Dosage and Administration (Cont’d) Dosage in patients with normal renal function

23. Dosage and Administration (Cont’d) Dosage Adjustment in Adult Patients with Renal Impairment (cr clearance <50 mL/min)
Cr clearance : urine cr * GFR /plasma cr

24. Drug Interactions
It is recommended to adjust the other drugs rather than antimicrobial agent.

26. 2012 Update on Antimicrobial Susceptibility SENTRY Antimicrobial Surveillance Program

27. SENTRY 2012 - Antimicrobial susceptibility trends among streptococcus pneumoniae-1

28. SENTRY 2012 - Antimicrobial susceptibility trends among streptococcus pneumoniae-2

29. Box AND BLISTER 500mg

30. BOX AND BLISTER 750mg

32. VIRABEX indications and dosage (FDA approved &OFF label)
IWHO medical department

33. FDA approved

34. FDA approved Indication
Suppressive therapy in immuno-compromised patients is strongly recommended;
(in HIV+ patients reccurent episodes are more severe and virus shedding is more common. on one hand when anti HSV regimen is added to anti retro virus regimens HIV-RNA level is lower at plasma and vaginal secretions.)
Dosage
VIRABEX 500mg /BID/PO
ACYCLOVIR mg /BID or TID/ PO

35. OFF label Indication: Dental procedures Prophylaxis
Dermatologic procedures prophylaxis:
Chemical peeling
Laser Resurfacing(ablative)
Laser Hair removal
Butolinum Toxin and Gel injection
Microdermabrasion
Dosage:
VIRABEX mg /BID/PO/ a few hours or one day before
treatment for at least 5-7 days or until Epidermal resurfacing
(2 weeks)
Acyclovir 400mg/TID/PO or 800mg/BID/PO or 200mg /5X/PO
with the same duration as VIRABEX.

36. OFF label
Indication:
Genital herpes prophylaxis before herniated disc operation
Oro-facial herpes prophylaxis before trigeminal nerve decompression
Dosage:
VIRABEX mg/BID/PO, 2 days before until 3-7 days post-operation
ACYCLOVIR 400mg/TID or 800mg/BID or 200mg/5X, 2 days before until 3-7 days post-operation

37. OFF label Indication Suppressive therapy in immuno-competent patients:
recurrent orolabial herpes more than 6 episodes in a year or
severe and painful lesions
Severe systemic complications: Meningitis, Eczema herpeticum,
erythema multiform, ocular herpes, pneumonitis,
esophagitis,
Dosage
VIRABEX mg/q day for 6 to 18 month
ACYCLOVIR 400mg BID/PO for 6 to 18month

38. OFF label
Indication
Ocular herpes; due to different types of manifestations and severity IV or Oral treatments will be adjusted (keratitis could be treated with oral forms), other ocular manifestations generally should be set on IV treatment)
Dosage
VIRABEX 1000mg/TID/ days
ACYCLOVIR 400mg/5X/14-21 days

39. OFF label Indication Systemic Complications Treatment;
Herpetic Encephalitis, Meningitis, Disseminated infection,
Esophagitis, Pneumonitis
Dosage
(severe forms of these complications have poor prognosis and mortality rate is high even with IV treatments)
ACYCLOVIR mg/kg/TID/IV
(in some mild cases of pneumonitis or esophagitis oral treatment could be considered)
VIRABEX 1000mg/TID/PO days

40. OFF label Indication Pediatric orolabial lesions
First episode ( gingivo-stomatitis , pharyngitis)
Recurrent episodes
Dosage
First episode:
ACYCLOVIR 5mg/kg/IV/TID for 7 days
ACYCLOVIR 15mg/kg/5X/for 7 days
VIRABEX 20mg/kg/TID/for 7 days
VIRABEX 20mg/kg/dose/BID (max1000mg/dose)
for one day

41. OFF label Indication Oro facial lesions in immuno-compromised patients
Dosage
First episode
VIRABEX 1000mg/BID/Po for 14 days or until lesions resolved
ACYCLOVIR 400mg/4X/Po for 14 days or until lesions resolved
Recurrent episodes
VIRABEX 1000mg/BID/Po for 10 days or until lesions resolved
ACYCLOVIR 400mg/TID/Po for 10 days or until lesions resolved

42. OFF label
Indication
CMV prophylaxis in patients, post organ transplantation
Dosage
VAL-GANCYCLOVIR for 1 month and then VIRABEX 2000mg/QID for 2 month
(in patients who receive CMV prophylaxis regimen there is no need to anti HSV or VZV prophylaxis regimen)

43. OFF label Indication Herpes Gladiatorum Eczema Herpeticum Doseage
VIRABEX 500mg/BID for 7 to 10 days
ACYCLOVIR mg /5x for 7 to 10 days

44. OFF label Indication Bells palsy Sudden Sensory neural hearing loss
Dosage
VIRABEX 1000mg/BID for 7 days
ACYCLOVIR mg /TID or QID for 7 days

45. OFF label Indication Pityriasis Rosea
(an acute self limited infection with papulo-scuamous lesions on the trunk and proximals. Viral etiology is hypothesized with HHV7, HHV8
Dosage
ACYCLOVIR 800mg/5X /PO for one week
VIRABEX 1000mg/ TID for one week

46. Dose adjustment
To mimic an IV ACYCLOVIR regimen of 10mg/kg/dose/ TID , VIRABEX with dose of 30mg/kg/dose/TID can be considered.
To mimic a PO ACYCLOVIR regimen of 20mg/kg/dose/5X , VIRABEX with dose of 20mg/kg/dose/TID can be considered
Harriet Lane Handbook 20th edition 2016

48. Thanks for your attention