This document discusses quinolones, a class of broad-spectrum antibiotic drugs. It provides details on their mechanism of action, examples of different generations of quinolones, and their pharmacokinetic properties. The document also discusses common side effects and important drug interactions with quinolones like antacids and warfarin. Approaches for managing drug interactions are presented, such as timing doses appropriately. Overall recommendations emphasize scheduling quinolones to avoid interactions and using ones with fewer drug interaction risks.

1. A
Clinical Presentation at IBBSH, Minna
July 2013
By
Umar’ M. Danjuma
B.pharm

2. Introduction
 Quinolones; are family of broad spectrum antibiotics, the
term quinolone(s) refers to potent synthetic
chemotherapeutic agent.
 They act by preventing bacteria DNA from unwinding &
duplicating thus preventing replication via the inhibition
of bacteria DNA gyrase or the topoisomerase II enzymes.
 The fluoroquinolones are bactericidal antibiotics & they
exhibit a post-antibiotic effect following bacterial
exposure to inhibitory concentrations. The antibacterial
effect continues for approximately 2 to 3hrs after bacteria
are exposed to these drugs, despite sub-inhibitory
concentrations.

3.  They are active against both Gram +ve & Gram -ve bacteria
particularly Salmonella, Shingella, Campylobacter, neisseria,
Bacillus anthracis, pseudomonas, also Chlamydia & some
mycobacteria.
 Majority of quinolones are floroquinolones, with a Flourine atom
attach to the central ring system & usually at c-6 or c-7
 The addition of fluoride to the original quinolone antibiotic
makes the fluoroquinolones have a broader antimicrobial
spectrum and improved pharmacokinetic properties.
 Enhanced antimicrobial activity has extended the use of the
fluoroquinolones beyond the traditional indications for quinolone
antibiotics in the treatment of urinary tract infections.
 The fluoroquinolones are effective in a wider variety of infectious
diseases, including skin and respiratory infections.

4.  Because of their excellent safety and tolerability, they have
become popular alternatives to penicillin and cephalosporin
derivatives in the treatment of various infections.
 With respect to this facility; they are the Drug of choice for
enteric fever & urinary tract infections.
 2 out of 3 patients are being prescribed a quinolone with or
with-out lab. results. Thus, they are the most frequently
prescribed antibiotic, so it is very important we know how
best to use these drugs to achieve optimum benefits.

5. Examples of quinolones
 1st generation_ cinoxacin, nalidic acid, rosoxacin.
 2nd generation_ ciprofloxacin, norfloxacin, ofloxacin,
pefloxacin, enofloxacin, lemofloxacin e.t.c.
 3rd generation_ balofloxacin, levofloxacin,,
sparfloxacin, temafloxacin,
 4th generation_ clinafloxacin, gatifloxacin,
moxifloxacin, prulifloxacin, trovafloxacin.
 New members include garenoxacin, dalafloxacin.

6. Pharmacokinetic Parameters
 The newer fluoroquinolones are rapidly and almost
completely absorbed from the gastrointestinal tract.
 Peak serum concentrations obtained after oral
administration and are very near those achieved with
intravenous administration.
 Consequently, the oral route is generally preferred in most
situations, and hospitalized patients should be switched
from intravenous to oral formulations as soon as oral
medications can be tolerated.
 Absorption of orally administered fluoroquinolones is
significantly decreased when these agents are co-
administered with aluminum, magnesium, calcium, iron or
zinc, because of the formation of insoluble drug cationic
chelate complexes in the gastrointestinal tract.

7.  They have a large volume of distribution, thus concentrate in
tissues at levels that often exceed serum drug concentrations.
 Penetration is particularly high in renal, lung, prostate,
bronchial, nasal, gall bladder, bile and genital tract tissues.
 Urine drug concentrations of some fluoroquinolones, such as
ciprofloxacin and ofloxacin may be as much as 25 times higher
than serum drug concentrations.
 Consequently, these agents are especially useful in treating
urinary tract infections.
 the newer fluoroquinolones have long half-lives thus allow
once- or twice-daily dosing.

8. Side Effects
 They are well tolerated, the most common adverse
effects of fluoroquinolones involve the gastrointestinal
tract and include nausea, vomiting and diarrhea, which
occur in 3 to 6 percent of patients.
 Other more serious but less common side effects are
central nervous system effects (headache, confusion and
dizziness),
 phototoxicity (more common with lomefloxacin and
sparfloxacin
 cardiotoxicity (sparfloxacin) and
 hepatotoxicity (trovafloxacin) .

9. Intro cont’d
 Concern about the adverse effects of quinolones on joints is
based primarily on experimental evidence in young animals.
These drugs are not recommended for use in patients
younger than 18 years or in pregnant or lactating women.
 however, in one study no arthropathies were observed in
more than 1,000 children who received ciprofloxacin.
 these popular antimicrobial agents are associated with
several clinically significant drug interactions, which can
either lead to dramatic reduction of serum quinolone
concentration or inhibition of the metabolism of certain
drugs which can be very dangerous to the patient e.g.
warfarin & theophylline.

10. Sample prescriptions
 Patient M.N, adult male
 Rx,
 Tab. Coartem iv bd 3/7
 Tab. Pcm ii tds 3/7
 Tab. Ciprofloxacin 500mg bd 5/7
 Susp. Antacid 20ml tds 1/52

11.  Patient Y. Q
 Adult fm,
 Rx,
 Tab. Ciprofoxacin 500mg bd 1/52
 Tab. Pcm ii tds 3/7
 cap. Ferobin plus I bd 2/52

12.  Patient O. S
 Adult male
 rx,
 Tab. Metformin 500mg tds 2/52
 Tab. Daonil 10mg o.d 2/52
 Tab. Ciprofloxacin 500mg bd 5/7
 Tab. Pcm ii tds 3/7

13. Possible interactions with
quinolones
• Magnesium/Aluminum antacids can cause dramatic
decrease of up to 85% serum conc. of ciprofloxacin
when given 5 to 10 minutes before the quinolone.
 Sucralfate can cause a 90% reduction of serum conc. if
taken together.

14. interactions cont’d
 Iron products, studies demonstrated 60% reduction of
ciprofloxacin.
 Enteric feeding products also reduces conc. because
they contains divalent cat-ions
 Calcium products; dairy products also causes reduction
but interestingly they have less impressive effect on the
bioavailability of quinolones. In fact, with newer
quinolones e.g levofloxacin & gatifloxacin , the effect
appears to be negligible.
 Zinc; also not as clinically important as Mg/Al. antacids
also cause reduction.

15. Other quinolone interactions
 Theophylline; increase theophylline serum conc. &
toxicity is associated with enoxacin, ciprofloxacin, &
norfloxacin.
 Warfarin; increase PT/INR, but more likely at higher
doses & more common with elderly.
 Caffeine; increase caffeine serum conc.; result in
nausea & vomiting.
 Glibenclamide, enhances hypoglycemic effect.
 Ibuprofen, possibly increase the rick of convulsion

16. Approaches to managing
Quinolones drug interaction
 Antacids, the interaction is best avoided by admin. the
quinolone 2hrs. before the antacid or 6hrs. after.
 Sucralfate, if the quinolone is prescribed 2ce-daily &
sucralfate can not be discontinued, schedule 12hrs
rather than 6hrs to increase the interval between
doses. e.g. give quinolone at 6am & 6pm and sucralfate
at 8am & 8pm.
 Iron product, circumvent by prescribing the quinolone
2hrs before the iron product.

17.  Calcium (dairy products), it is important to give the
quinolone 2hrs before any calcium containing products
–including dairy foods i.e. milk & yogurt
 Administration of quinolone 2hrs before zinc-
containing products e.g. zinc sulfate, cold lozenges &
multivitamins does enhances bioavailability.
 Enteric feeding, if the quinolone requires once-daily
dosing, with-holding tube feeding for 2hrs before and
after admin. of the antimicrobial agent is reasonable.

18.  Theophylline, circumvent interaction by using an
appropriate quinolone that does not affect theophylline
metabolism such as ofloxacin, levofloxacin, gatifloxacin
or moxifloxacin; if a quinolone that increase serum
theophylline concentration must be used, verify
theophylline level at baseline and monitor.
 Caffeine, also circumvent by using alternatives such as
ofloxacin or levofloxacin, and avoid ciprofloxacin and
enoxacin; alternatively, reduce caffeine consumption if
>/= 200mg/day.
 Warfarin, monitor PT/INR; and anticipate possible need
to adjust warfarin dosage when initiating or
discontinuing quinolones

19. Recommendations
 Quinolones should be scheduled at 6am and 6pm as a
default then other drugs at least 2hrs. after
 Interactions can frequently be circumvented by use of
Quinolones that has minimal or no effect on the
metabolism of drugs such as theophylline and warfarin
e.g levofloxacin, gatifloxacin and moxifloxacin
 alternatively other relatively effective antimicrobial
agents from other class should be used.

20. THANK U ALL FOR LISTENING

21. references
 Bianco TM, Bussey HI, et al. Potential warfarin-
ciprofloxacin interaction in patient receiving long-
term anticoagulant.1992.
 Bnf-56 quinolones interactions
 Hooper DC, Wolfson JS. Floroquinolones
antimicrobial agents. 1991
 Timothy H. Quinolones: keys to reducing the risk of
interactions. University of tennessee. Ranbaxy’s
Med+mag. Vol. 2E Issue 11.
 Wikipedia, the free encyclopedia quinolones