GENERATIONS OF QUINOLONES

 First-generation : Nalidixic Acid

 Second-generation: Ciprofloxacin,
Ofloxacin, Norfloxacin
 Third-generation: Levofloxacin, Sparfloxacin
 Fourth-generation: Gatifloxacin,
Moxifloxacin
 Amongst these the drugs most frequently
prescribed today consist of
Moxifloxacin,Ciprofloxacin & Levofloxacin .
 Moxifloxacin was developed by Bayer AG.
 It is marketed worldwide under the brand
names Avelox, Avalox, and Avelon for oral
treatment.
 Moxifloxacin was approved by USFDA in 1999.
 In most countries, the drug is also available
in parenteral form for intravenous infusion.
 Ranking 140th within the top 200 prescribed
drugs in the United States for 2007
moxifloxacin, in the same manner as
ciprofloxacin, has proven to be a blockbuster
drug for Bayer A. G., generating billions of
dollars in additional revenue.
 In 2007 alone, Avelox generated sales of
$697.3 million dollars worldwide.
 Moxifloxacin is also sold in an ophthalmic
solution (eye drops) under the brand names
Vigamox, Moxeza for the treatment of
conjunctivitis (pink eye).
 Moxifloxacin is currently marketed in more
than 80 countries worldwide.
 The European Union requires that
moxifloxacin only be prescribed when other
antibiotics that have been initially
recommended for treatment cannot be used
or have failed.
 At the current time, there are no approved
uses within the pediatric population for Oral
and I.V. moxifloxacin. A significant number of
drugs found within this class, including
moxifloxacin, are not licensed by the FDA for
use in children due to the risk of permanent
injury to the musculoskeletal system.
 Prescribing moxifloxacin to treat an
unapproved use (other than those listed
above) within the pediatric, as well as the
adult population, does however take place
rather frequently.
 In the European Union, it is licensed for
acute bacterial exacerbations of chronic
bronchitis, non-severe community-acquired
pneumonia, and acute bacterial sinusitis.
 Based on its investigation into reports of rare
but severe cases of liver toxicity and skin
reactions, the European Medicines Agency
recommended in 2008 that the use of the
oral (but not the IV) form of moxifloxacin be
restricted to infections in which other
antibacterial agents cannot be used or have
failed.In the US, the marketing approval does
not contain these restrictions, though the
label contains prominent warnings against
skin reactions.
CLINICAL PHARMACOLOGY

 MOXIQUIN is a member of the

fluoroquinolone class of antibacterial
agents.
 MOXIQUIN is a fourth generation synthetic
fluoroquinolone antibiotic agent.
 It has in vitro activity against a wide range of
Gram-positive, Gram-negative, atypical and
anaerobic pathogens.
STRUCTURE OF MOXIFLOXACIN
HYDROCHLORIDE
SUSCEPTIBLE BACTERIA
 A broad spectrum of bacteria is susceptible
including, but not limited to:
 Staphylococcus aureus
 Staphylococcus epideridis
 Streptococcus pneumoniae
 Haemophilus infuenzae
 Klebsiella spp.
 Moraxella catarrhalis
 Enterobacter spp.
 Mycobacterium spp.
 Bacillus anthrais
MECHANISM OF ACTION
 The bactericidal action of results from the
inhibition of both type II topoisomerases
(DNA gyrase and topoisomerase IV) required
for bacterial DNA replication, transcription
and repair.
PHARMACOKINETICS

 Absorption
 Moxifloxacin, given orally is well absorbed
from the gastrointestinal tract. The absolute
bioavailability of moxifloxacin is
approximately 90 percent.
 Co-administration with a high fat meal does
not affect the absorption of moxifloxacin.
 Distribution
 Moxifloxacin is approximately 30-50% bound
to serum proteins, independent of drug
concentration.
 Moxifloxacin is widely distributed throughout
the body, with tissue concentrations often
exceeding plasma concentrations.
 Moxifloxacin has been detected in the saliva,
nasal and bronchial secretions, mucosa of
the sinuses, skin blister fluid, subcutaneous
tissue, skeletal muscle, and abdominal
tissues and fluids following oral or
intravenous administration of 400 mg.
 Metabolism
 Approximately 52% of an oral or intravenous
dose of moxifloxacin is metabolized via
glucuronide and sulfate conjugation.
 The cytochrome P450 system is not involved
in moxifloxacin metabolism, and is not
affected by moxifloxacin. The sulfate
conjugate (M1) accounts for approximately
38% of the dose, and is eliminated primarily
in the feces.
 Approximately 14% of an oral or intravenous
dose is converted to a glucuronide conjugate
(M2), which is excreted exclusively in the
urine. Peak plasma concentrations of M2 are
approximately 40% those of the parent drug,
while plasma concentrations of M1 are
generally less than 10% those of
moxifloxacin.
 In vitro studies with cytochrome (CYP) P450
enzymes indicate that moxifloxacin does not
inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19,
or CYP1A2, suggesting that moxifloxacin is
unlikely to alter the pharmacokinetics of
drugs metabolized by these enzymes.
 Excretion
 Approximately 45% of an oral or intravenous
dose of moxifloxacin is excreted as
unchanged drug (~20% in urine and ~25% in
feces).
 A total of 96% ± 4% of an oral dose is
excreted as either unchanged drug or known
metabolites. Elimination half life of 12
hours.
CONTRAINDICATIONS

 Patients with hypersensitivity to

moxifloxacin, other quinolones or to any of
the excipients
 Patients who are pregnant or lactating
 Patients below 18 years of age
WARNINGS AND PRECAUTIONS

 Female and elderly patients who may be more

susceptible to the effects of QTc-prolonging drugs
 Patients with liver cirrhosis as pre-existing QT
prolongation cannot be excluded
 Patients receiving drugs that prolong the QT interval
(e.g. cisapride, erythromycin, antipsychotics and
tricyclic antidepressants)
 Patients with ongoing proarrhythmic conditions, such
as significant bradycardia or acute myocardial
ischemia
 Patients with CNS disorders which may predispose to
seizures or lower the seizure threshold
 Patients with myasthenia gravis
ADVERSE REACTIONS

 The commonly reported adverse events are:

mycotic superinfections; headache;
dizziness; QT prolongation in patients with
hypokalaemia; nausea; vomiting;
gastrointestinal and abdominal pains;
diarrhoea; increase in transaminases level.
DRUG INTERACTIONS

 Antacids, Sucralfate, Multivitamins and other

products containing Multivalent Cations
 MOXIQUIN should be taken at least 4 hours
before or 8 hours after these agents.
 Warfarin: MOXIQUIN enhance the anticoagulant
effects of warfarin
 Nonsteroidal Anti-Inflammatory Drugs
(NSAIDs):may increase the risks of CNS
stimulation and convulsions .
 Drugs that Prolong QT:MOXIQUIN should be
avoided with Class IA and Class III
antiarrhythmics.
USE IN SPECIIFIC POPULATIONS

 Pregnancy: Category C
 Nursing Mothers: Contraindicated
 Pediatric Use : Contraindicated in less
than 18 years..
 Geriatric Use: There were no clinically
significant differences in most adverse
events reported by patient groups ≥ 65 years
old and < 65 years old.
 Gender:Dosage adjustments based on gender are not
necessary.
 Elderly:Dosage adjustments based on age are not necessary.
Also adult patients with lower body weight do not need dose
adjustment.
 Hepatic Impairment: Based on the pharmacokinetic data, no
dosage adjustment is required for patients with mild or
moderate hepatic insufficiency . Due to limited clinical data,
the use of Moxifloxacin is not recommended in patients with
severe hepatic insufficiency .
 Renal Impairment: No dosage adjustment is required in
patients with renal impairment (including creatinine clearance
≤ 30 ml/min/1.73m2) and in patients on chronic dialysis (i.e.
haemodialysis or continuous ambulatory peritoneal dialysis).
  
OVERDOSAGE

 Single oral overdoses up to 2.8 g were not

associated with any serious adverse events. In
the event of acute overdose, the stomach
should be emptied and adequate hydration
maintained. ECG monitoring is recommended
due to the possibility of QT interval
prolongation.
 The patient should be carefully observed and
given supportive treatment. The administration
of activated charcoal as soon as possible after
oral overdose may prevent excessive increase
of systemic moxifloxacin exposure.
INDICATIONS AND USAGE

MOXIQUIN 400 mg tablets are indicated for the

treatment of:
 Community acquired pneumonia (CAP),
 Acute exacerbations of chronic bronchitis
(AECB),
 Acute bacterial sinusitis (ABS),
 Complicated skin and skin structure infections
(cSSSI),
 Pelvic inflammatory disease (PID), and
 Complicated intra-abdominal infections
(cIAI).
DOSAGE AND ADMINISTRATION

Infection Daily Dose Route of Usual Duration

Administration

Community Acquired Pneumonia (CAP) 400mg PO 10 days

(Mild/Moderate)

Acute Exacerbation of Chronic Bronchitis 400mg PO 5-10 days

(AECB)

Acute Bacterial Sinusitis (ABS) 400mg PO 7 days

Mild to Moderate Pelvic Inflammatory 400mg PO 14 days

Disease (PID)

Community Acquired Pneumonia (CAP) 400mg IV/PO 7-14 days

Complicated Skin and Skin Structure 400mg IV/PO 7-21 days

Infections (cSSSI)

Complicated Intra-abdominal Infections 400mg IV/PO 5-14 days

(cIAI)
 The recommended dose for MOXIQUIN 400mg
tablet is once daily (od) for all
indications.MOXIQUIN 400 mg can be taken
without regard to food.
  CONCLUSION:
 Moxifloxacin-based triple therapies showed
HIGH ERADICATION RATE OF H. PYLORI WITH MOXIFLOXACIN-BASED TREATMENT: A RANDOMIZED CONTROLLED TRIAL .

higher eradication rates with few side effects

and good drug compliance when compared
with standard H. pylori treatments.
Moreover, the increased prevalence of
clarithromycin resistance suggests that
moxifloxacin-based regimens could be safe
and effective options in treatment of H.
pylori infection.
 PMID:17634896
MOXIFLOXACIN: A RESPIRATORY FLUOROQUINOLONE.

 RESULTS:
 The clinical efficacy of moxifloxacin has been shown in
controlled studies of community-acquired pneumonia,
exacerbations of chronic bronchitis and acute bacterial
rhinosinusitis. Moxifloxacin has demonstrated a faster
resolution of symptoms in community-acquired pneumonia
and exacerbations of chronic bronchitis patients compared
with first-line therapy together with excellent eradication
rates.
 CONCLUSIONS:
 The use of moxifloxacin as first-line therapy for moderate to
severe respiratory infections in the community and the
hospital has been recognized in international guidelines.
 PMID:18570608
MOXIFLOXACIN IN RESPIRATORY
TRACT INFECTIONS.
 It has also demonstrated better eradication
in exacerbations of CB compared with
standard therapy, in particular the
macrolides.
 PMID:15757424
THE MOXIFLOXACIN IN ACUTE
EXACERBATIONS OF CHRONIC BRONCHITIS
TRIAL (MAESTRAL)
 The MAESTRAL study showed that
moxifloxacin was as effective as
amoxicillin/clavulanic acid in the treatment
of outpatients with AECOPD. Both therapies
were well tolerated.
 patients received moxifloxacin 400 mg p.o.
O.d. (5 days) or amoxicillin/clavulanic acid
875/125 mg p.o. b.i.d. (7 days).
 http://www.ncbi.nlm.nih.gov/pmc/
articles/PMC2695197/
MOXIFLOXACIN & LEVOFLOXACIN
AGAINST S. PNEUMONIAE
 Moxifloxacin is 4- to 10-fold more active than
levofloxacin against S. pneumoniae. A greater
intrinsic activity is linked with faster
eradication and reduced susceptibility of the
development of resistance. In fact, some
reports have described the development of
resistance of S. pneumoniae during treatment
with levofloxacin (Davidson et al 2002), but
no reports have shown the same phenomenon
in patients treated with more active
fluoroquinolones such as moxifloxacin or
gatifloxacin.
 Therefore, these findings support the
concept of “use the best first”. The most
potent agent of the class should be used as
first line therapy to avoid the development
of resistance to the entire class of
antimicrobials, particularly in moderate to
severe cases or those with risk factors for
relapse or poor compliance.
 Eradication rates for H. influenzae in
exacerbations of CB treated with
moxifloxacin or macrolides. Ref: Niederman
et al (2006).
SIEGERT STUDY
 Comparison of Moxifloxacin 400 mg OD for 7
days with Cefuroxime-axetil 250 mg BD for
10 days.
VIRTUOUS CIRCLE
 Priced at Rs 95.00/tablet.

 And Now for the patient health and

economy, we have revised the price of
Moxiquin.

i.e
@ RS 40 per tab
DETAILING TEXT
 With immense pleasure ASIAN presents you
with MOXIQUIN the First brand of
Moxifloxacin 400 mg tablet in Nepal.
 Dr. Win over tough infections with
MOXIQUIN.
 In tough infections like Respiratory
infections, Complicated Intra-abdominal
infections, Pelvic Inflammatory diseases &
Complicated skin and skin structure
infections…Use the Best First…MOXIQUIN…
with Once Daily (O.D)benefits.
 MOXIQUIN is “The Respiratory Antibiotic” as it
has Bioavailability of approximately 91%,
excellent pulmonary tissue penetration,
excellent concentration in alveolar
macrophages and rapid distribution in extra
vascular spaces.
 Dr. According to MAESTRAL study Moxifloxacin
400 mg OD 5 days is as effective as
Amoxicillin/Clavulanic acid 875/125 mg B.D 7
days in the treatment of Acute Excerbations
of Chronic Obstructive Pulmonary Disease.
(Source provided)
 Dr. SIEGERT study compared Moxifloxacin 400 mg
OD 7days with Cefuroxime-axetil 250mg BD 10
days, the clinical cure rate was 96.7% for
Moxifloxacin and 90.7% for Cefuroxime-axetil.
(Source provided).
 Similarly, the comparison of Moxifloxacin with
Azithromycin revealed an eradication rate of 96.8%
with Moxifloxacin and 84.6% with Azithromycin.
 The comparison of Moxifloxacin with
Clarithromycin revealed an eradication rate of
90.1% with Moxifloxacin and 64.3% with
Clarithromycin.
 Dr. According to “Virtuous Circle of antibiotic
treatment in acute exacerbations of CB and
COPD” by De Benedetto and Sevieri: Use of
Moxifloxacin in COPD results in Fast bacterial
killing,complete eradication and
immunomodulatory activity- thus few days with
bacteria—reduce imflammation ---reduce organ
damage which results in Less frequent
exacerbations, better preserved pulmonary
function, improved HRQol, less need for
symtomatic treatment, fewer hospitalization
and thus overall reduction in healthcare costs.
 The dosage and administration is as follows:

Dr. Please prescribe MOXIQUIN which

ENSURES COMPLETE CURE &COMPLIANCE.
 Each film coated tablet of MOXIQUIN
contains Moxifloxacin Hydrochloride USP
equivalent to Moxifloxacin 400 mg.

 Available in a inner cartoon in a strip of 1X5.

 Available in a box of 1X5X10’s.
 Priced at Rs 95/tablet.
 Revised price @ 40/tab
LAUNCHING STRATEGY
 As this is a Image Enhancing Product for ASIAN we
will promote and inform the launching of MOXIQUIN
to all the Medical fraternity.
 Prepare a list of Chest Physicians of your area.
 Also include Early-adapter Doctors and KOLs
(Knowledge Opinion Leaders).
 Initially we will focus in this list of doctors.
 We will visit the focused doctors in groups.
 Provide them with literatures and research articles.
 Promotional input in first visit will include LBC,
Pilot-pen, Chocolate.
 After one-week we will visit with a Gift.
 Strength Opportunity

 First brand in Nepal  Still heavy promotion

is required.
 Target oriented Product i.e respiratory  In house parenteral
antibiotics form is unavailable.
 Have to break the
 Higher antibiotics, prestigeous impression of
product,Value building product expensiveness.
 Contraindicated below
 Patient copliance, OD benefit. 18 years
 Poor compititor.  Some side effects.

 Now Parenteral also available.  One player has just

 Economic compared to Amoxy+Clav entered the market
with bonus.
 Truste of physicians and surgeon.