keys to reducing interactions with quinolones

keys to reducing Quinolones interactions

A

Clinical Presentation at IBBSH, Minna

July 2013By

Umar’ M. Danjuma B.pharm

IntroductionQuinolones; 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.

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. 

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.

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.

Pharmacokinetic ParametersThe 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.

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.

Side EffectsThey 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) andhepatotoxicity (trovafloxacin) .

Intro cont’dConcern 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.

Sample prescriptionsPatient M.N, adult maleRx,Tab. Coartem iv bd 3/7Tab. Pcm ii tds 3/7Tab. Ciprofloxacin 500mg bd 5/7Susp. Antacid 20ml tds 1/52

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

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

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.

interactions cont’dIron products, studies demonstrated 60%

reduction of ciprofloxacin.Enteric feeding products also reduces conc.

because they contains divalent cat-ionsCalcium 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.

Other quinolone interactionsTheophylline; 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

Approaches to managing Quinolones drug interactionAntacids, 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.

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.

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

RecommendationsQuinolones 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.

THANK U ALL FOR LISTENING

referencesBianco TM, Bussey HI, et al. Potential

warfarin-ciprofloxacin interaction in patient receiving long-term anticoagulant.1992.

Bnf-56 quinolones interactionsHooper DC, Wolfson JS. Floroquinolones

antimicrobial agents. 1991Timothy 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