1.AVELOX HISTORY
(How was Avelox discovered?)

Moxifloxacin is a synthetic flouroquinolone antibiotic agent. Bayer AG developed the drug and sells it worldwide under the brandname Avelox for oral treatment. Each tablet contains 400mg Moxifloxacin.

The US FDA approved Avelox in November 2001.

Bayer is a wholly owned subsidiary of Bayer AG, based in Leverkusen, Germany, one of the largest industrial concerns in the world. Comprised of about 350 companies, the Bayer Group has subsidiaries or agents in approximately 150 countries.

Bayer's products are as follows:

• Bayer HealthCare
• Animal Health
• Biological Products
• Consumer Care
• Diagnostics
• Pharmaceutical
• Bayer MaterialScience
• Coating, Adhesive & Sealant Raw Materials
• Inorganic Basic Chemicals
• Polycarbonates
• Polyurethanes
• Thermoplastic Polyurethanes (TPU)

Note: World-drugs.net sells generic version of Avelox

2.AVELOX FACTS

Avelox is a type of medicine known as a quinolone antibiotic. Avelox is used to treat infections of the airways caused by bacteria.

Avelox works by entering bacterial cells and inhibiting the action of two bacterial enzymes, called topoisomerase II (DNA-gyrase) and IV. These enzymes are involved in the replication and repair of bacterial genetic material (DNA); processes that are needed for the bacteria to multiply.

The inhibition of these bacterial enzymes and hence the interference with the bacterial DNA, ultimately results in Avelox killing the bacteria.

3.ABOUT AVELOX MEDICATION

What are antibiotics?

An antibiotic is a drug that kills or slows the growth of bacteria. Antibiotics are one class of "antimicrobials", a larger group, which also includes anti-viral, anti-fungal, and anti-parasitic drugs. They are relatively harmless to the host, and therefore can be used to treat infections. The term originally described only those formulations derived from living organisms, in contradistinction to "chemotherapeutic agents", which were purely synthetic. Nowadays the term "antibiotic" is also applied also to synthetic antimicrobials, such as the sulfonamides.

Antibiotics are labeled as "magic bullets": drugs, which target disease without harming the host. Antibiotics are not effective in viral, fungal and other nonbacterial infections, and individual antibiotics vary widely in their effectiveness on various types of bacteria. Some specific antibiotics target either gram-negative or gram-positive bacteria, and others are more wide-spectrum antibiotics.

The effectiveness of individual antibiotics varies with the location of the infection, the ability of the antibiotic to reach the site of infection, and the ability of the bacteria to resist or inactivate the antibiotic. Some antibiotics actually kill the bacteria (bactericidal), whereas others merely prevent the bacteria from multiplying (bacteriostatic) so that the host's immune system can overcome them.

Classes of Antibiotics?

There are many ways to classify antibiotics.

One such classification is by chemical structure:

Aminoglycosides

• Amikacin
• Dibekacin
• Gentamicin
• Kanamycin
• Neomycin
• Netilmicin
• Paromomycin
• Sisomycin
• Streptomycin
• Tobramycin

 

Beta-lactam ring antibiotics

• Carbapenems
• Ertapenem
• Imipenem
• Meropenem

Cephalosporins and cephamycins

• Cephalexin
• Cefazolin
• Cefuroxime
• Cefadroxil
• Ceftazidime

Penicillins

• amoxicillin

Monocyclic beta-lactams

Glycopeptide antibiotics

• Vancomycin
• Teicoplanin
• Ramoplanin
• Decaplanin

Oxazolidinones

• Linezolid
• Quinupristin/dalfopristin

Polyketides

Macrolides

• Erythromycin
• Azithromycin
• Clarithromycin
• Roxithromycin

Ketolides

• Telithromycin

Tetracyclines

• Doxycycline
• Oxytetracycline
• Chlortetracycline  

Polymyxins

• Polymyxin B
• Colistin  

Quinolones (fluoroquinolones)

• Nalidixic acid
• Ciprofloxacin
• Ofloxacin
• Norfloxacin
• Moxifloxacin
• Levofloxacin
• Trovafloxacin

Streptogramins

Sulfonamides

• Prontosil 

Other important antibiotics:

• Chloramphenicol
• Clindamycin
• Fusidic acid
• Trimethoprim

Another such classification is by their mechanism of action

Antibiotics, which interfere with cell-wall synthesis

Beta-lactams, including penicillins like amoxicillin and cephalosporins; mono-lactams, such as Imipenem; vancomycin, bacitracin

Antibiotics that interfere with bacterial protein synthesis

Antibiotics that bind to the 50S ribosomal unit

Lincosamides/lincosides including clindamycin and lincomycin; chloramphenicol, macrolides

Antibiotics, which interfere the 30S ribosomal unit

Tetracyclines; aminoglycosides including gentamicin

Drugs that inhibit folate synthesis

Sulfonamides and trimethoprim

Drugs that interfere with DNA synthesis

Metronidazole, quinolones, novobiocin

Drugs that interfere with RNA synthesis

Rifampin (rifampicin)

Drugs that interfere with cell membrane function

Polymyxin B, gramicidin

Antibiotics can also be classified by the organisms against which they are effective, and by the type of infection in which they are useful, which depends on the sensitivities of the organisms that most commonly cause the infection and the concentration of antibiotic obtainable in the affected tissue.

Uses of Avelox

• Bronchitis
• Pneumonia

Pneumonia is defined as an inflammation, usually caused by infection of, involving the alveoli of the lungs. It occurs in patients of all age groups, but young children and the elderly, as well as immunocompromised and immune deficient patients, are especially at risk. Causal therapy is with antibiotics like amoxicillin.

• Skin or soft tissue infections

Cellulitis is a noncontagious inflammation of the connective tissue of the skin, resulting from a bacterial infection. Antibiotics like Avelox are given to control infection, and analgesics may be needed to control pain. Within 7 to 10 days of treatment cellulitis can be cured

4.AVELOX EFFECTIVENESS
(When is Avelox best taken?)

Absorption

Avelox given as an oral tablet, is well absorbed from the gastrointestinal tract. The absolute bioavailability of Avelox is approximately 90 percent. Co-administration with a high fat meal (i.e., 500 calories from fat) does not affect the absorption of Avelox. Consumption of 1 cup of yogurt with Avelox does not significantly affect the extent or rate of systemic absorption (AUC).

Distribution

Avelox is approximately 50% bound to serum proteins, independent of drug concentration. The volume of distribution of Avelox ranges from 1.7 to 2.7 L/kg. Avelox is widely distributed throughout the body, with tissue concentrations often exceeding plasma concentrations. Avelox has been detected in the saliva, nasal and bronchial secretions, mucosa of the sinuses, skin blister fluid, and subcutaneous tissue, and skeletal muscle following oral or intravenous administration of 400 mg. The rates of elimination of Avelox from tissues generally parallel the elimination from plasma.

Metabolism

Approximately 14% of an oral dose of Avelox 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 Avelox. In vitro studies with cytochrome (CYP) P450 enzymes indicate that Avelox 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 Avelox is excreted as unchanged drug (~20% in urine and ~25% in feces). A total of 96% ± 4% of an oral dose of Avelox is excreted as either unchanged drug or known metabolites. The mean (± SD) apparent total body clearance and renal clearance are 12 ± 2.0 L/hr and 2.6 ± 0.5 L/hr, respectively. 

5.AVELOX EFFECTS ON SPECIAL POPULATION
(How do different people react to Avelox?)

Geriatric

Following oral administration of 400 mg dose of Avelox for 10 days in 16 elderly (8 male; 8 female) and 17 young (8 male; 9 female) healthy volunteers, there were no age-related changes in Avelox pharmacokinetics. In 16 healthy male volunteers (8 young; 8 elderly) given a single 200 mg dose of oral Avelox, the extent of systemic exposure (AUC and Cmax) was not statistically different between young and elderly males and elimination half-life was unchanged. No dosage adjustment is necessary based on age.

Pediatric

The pharmacokinetics of Avelox in pediatric subjects has not been studied.

Gender

Following oral administration of 400 mg Avelox daily for 10 days to 23 healthy males (19-75 years) and 24 healthy females (19-70 years), the mean AUC and Cmax were 8% and 16% higher, respectively, in females compared to males. There are no significant differences in Avelox pharmacokinetics between male and female subjects when differences in body weight are taken into consideration.

A 400 mg single dose study was conducted in 18 young males and females. The comparison of Avelox pharmacokinetics in this study (9 young females and 9 young males) showed no differences in AUC or Cmax due to gender. Dosage adjustments based on gender are not necessary.

Race

Steady-state Avelox pharmacokinetics in male Japanese subjects were similar to those determined in Caucasians, with a mean Cmax of 4.1 µg/mL, an AUC24 of 47 µgh/mL, and an elimination half-life of 14 hours, following 400 mg p.o. daily.

6.AVELOX EFFECTS ON MEDICAL CONDITIONS
(How does Avelox affect your existing condition/ailment?)

Renal Insufficiency

The pharmacokinetic parameters of Avelox are not significantly altered in mild, moderate, severe, or end-stage renal disease. No dosage adjustment is necessary in patients with renal impairment, including those patients requiring hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD).

Hepatic Insufficiency

In 400 mg single oral dose studies in 6 patients with mild, and 10 patients with moderate, hepatic insufficiency, Avelox mean exposure (AUC) was 78% and 102%, respectively, of 18 healthy controls and mean peak concentration (Cmax) was 79% and 84% of controls. 

7.OTHER/ALTERNATE USES OF AVELOX
(What else does Avelox treat?)

Avelox may also be used to treat infections as prescribed by your physician.

8.ADVERSE/SIDE EFFECTS of AVELOX
(What are the side effects of Avelox?)

Clinical efficacy trials enrolled over 8,600 Avelox orally treated patients, of whom over 8,000 patients received the 400 mg dose. Most adverse events reported in Avelox trials were described as mild to moderate in severity and required no treatment. Avelox was discontinued due to adverse reactions thought to be drug-related in 2.9% of orally treated patients. The latter studies were conducted in community-acquired pneumonia and complicated skin and skin structure infections with, in general, a sicker patient population compared to the tablet studies.

Adverse reactions, judged by investigators to be at least possibly drug-related, occurring in greater than or equal to 2% of Avelox treated patients were: nausea (6%), diarrhea (5%), dizziness (2%). Additional clinically relevant uncommon events, judged by investigators to be at least possibly drug-related, that occurred in greater than or equal to 0.1% and less than 2% of moxifloxacin treated patients were:

Body as a whole : abdominal pain, headache, asthenia, injection site reaction (including phlebitis), moniliasis, pain, allergic reaction,

Cardiovascular : tachycardia, palpitation, vasodilation, QT interval prolonged, hypertension

Nervous System : insomnia, nervousness, vertigo, somnolence, anxiety, tremor,

Digestive : vomiting, abnormal liver function test, dyspepsia, dry mouth, flatulence, oral moniliasis, constipation, GGTP increased, anorexia, stomatitis, glossitis

Hemic And Lymphatic : leukopenia, eosinophilia, prothrombin decrease (prothrombin time prolonged/International Normalized Ratio (INR) increased), thrombocythemia, anemia

Metabolic And Nutritional : lactic dehydrogenase increased, amylase increased

Musculoskeletal : arthralgia, myalgia

Skin/Appendages : rash (maculopapular, purpuric, pustular), pruritus, sweating, urticaria

Special Senses : taste perversion

Urogenital : vaginal moniliasis, vaginitis, kidney function abnormal

Additional clinically relevant rare events, judged by investigators to be at least possibly drug-related, that occurred in less than 0.1% of Avelox treated patients were:

abnormal dreams, abnormal vision, agitation, amblyopia, amnesia, aphasia, arthritis, asthma, atrial fibrillation, back pain, chest pain, confusion, convulsions, depersonalization, depression, dysphagia, dyspnea, ECG abnormal, emotional lability, face edema, gastritis, gastrointestinal disorder, hallucinations, hyperglycemia, hyperlipidemia, hypertonia, hyperuricemia, hypesthesia, hypotension, incoordination, jaundice (predominantly cholestatic), lab test abnormal (not specified), leg pain, malaise, paraesthesia, parosmia, pelvic pain, peripheral edema, pseudomembranous colitis, prothrombin increase (prothrombin time decreased/International Normalized Ratio (INR) decreased), sleep disorders, speech disorders, supraventricular tachycardia, syncope, taste loss, tendon disorder, thinking abnormal, thrombocytopenia, thromboplastin decrease, tinnitus, tongue discoloration, ventricular tachycardia

Post-Marketing Adverse Event Reports:

Additional adverse events have been reported from worldwide post-marketing experience with Avelox. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events, some of them life-threatening, include anaphylactic reaction, anaphylactic shock, angioedema (including laryngeal edema), hepatitis (predominantly cholestatic), psychotic reaction, Stevens-Johnson syndrome, tendon rupture, and ventricular tachyarrhythmias (including in very rare cases cardiac arrest and torsade de pointes, and usually in patients with concurrent severe underlying proarrhythmic conditions).