Article: Moxifloxacin

Moxifloxacin
Systematic (IUPAC) name
1-cyclopropyl-7-[(1S,6S)-2,8-diazabicyclo [4.3.0]non-8-yl]-6-fluoro-8-methoxy-4-oxo- quinoline-3-carboxylic acid
Identifiers
CAS number	354812-41-2
ATC code	J01MA14
PubChem	152946
DrugBank	APRD00281
Chemical data
Formula	C21H24N3FO4
Mol. weight	401.431 g/mol
Pharmacokinetic data
Bioavailability	86 to 92%
Protein binding	30 to 50%
Metabolism	Glucuronide and sulfate conjugation Cytochrome P450 system not involved
Half life	12 hours
Excretion	Biliary and renal
Therapeutic considerations
Pregnancy cat.	C (US) B3 (Australia)
Legal status	Prescription Only
Routes	Oral, IV, local (eyedrops)

Moxifloxacin is a synthetic fluoroquinolone antibiotic agent. Bayer AG developed the drug and sells it worldwide (as the hydrochloride) under the brand name Avelox® (in some countries also Avalox®) for oral treatment. Each tablet contains 400mg. In most countries the drug is also available in parenteral form for intravenous infusion.

Mode of action

Like other fluoroquinolones, moxifloxacin inhibits the bacterial enzyme DNA gyrase (topoisomerase IV) and thus prevents supercoiling of bacterial DNA. This mechanism is lethal to susceptible bacteria. Moxifloxacin is often referred to as a chemotherapeutic drug because its mode of action has so far not been noted in any natural occurring or semi-synthetic antibiotic.

Distribution

Moxifloxacin is found in high concentrations in body tissues and fluids, such as saliva, nasal and bronchial secrets, sinus mucosa, skin blister fluid, subcutaneous and muscle tissues. There is good penetration into bone.^[1] Pus does not seem to inhibit the drug's potential to reach effective concentrations in infectious foci easily.

Susceptible bacteria

A broad spectrum of bacteria is susceptible including, but not limited to:

• Staphylococcus aureus
• Streptococcus pneumoniae
• Haemophilus influenzae
• Klebsiella spp.
• Moraxella catarrhalis
• Enterobacter spp.
• Mycobacterium spp.
• Bacillus anthracis

Pharmacokinetic behaviour in patients with decreased liver and renal function

Mild, moderate and severe renal dysfunction does not alter half-life, metabolization or excretion significantly. The same is true to for mild to moderate liver impairment (Child-Pugh class A and B). Nothing is known about severe liver impairment (Child-Pugh class C).

Uses

Moxifloxacin can be used to treat respiratory infections including acute sinusitis, acute exacerbations of chronic bronchitis and community-acquired pneumonia as well as skin and skin structure infections. Moxifloxacin is also used for the treatment of complicated intra-abdominal infections, as seen in hospitals and against acute mycobacterial infections (for example tuberculosis) as part of a multi-drug treatment regime. Since moxifloxacin is primarily metabolized and eliminate via the hepatic route, moxifloxacin is not indicated for the treatment of urinary tract infections.

In ophthalmology, moxifloxacin is available the form of eye drops, marketed by Alcon as Vigamox®, to treat conjunctival infections caused by susceptible bacteria.

Dosage

The dosage is 400 mg daily orally or via intravenous infusion (1 hour). The duration of treatment depends on the disease and ranges from 5 days in acute exacerbations of chronic bronchitis to 60 days for post-exposure prophylaxis of anthrax.

There is no sufficient clinical data about dosage to patients under 18 years of age. In geriatric patients no dose reductions are necessary.

Contraindication

Known hypersensitivity to moxifloxacin or any other ingredient of the preparation.

Pregnancy and lactation

• Pregnancy : Moxifloxacin has been assigned to class C.
• Lactation : Moxifloxacin is found in high concentration in the milk of breastfeeding mothers. Either the drug or the breastfeeding should be discontinued.

Side effects

Possible side effects include gastrointestinal tract disturbances (nausea, vomiting, anorexia, bloating, abdominal pain, diarrhea, and pseudomembranous colitis caused by Clostridium difficile), skin reactions (also Stevens-Johnson syndromAe), rhabdomyolysis, and serious heart problems (prolonged QT interval and torsades de pointes). Development of resistance has been noticed as well as rare cases of hepatotoxicity and seizures. Tendon rupture (including rupture of the Achilles tendon) can also occur.

Interactions

The concomitant intake of calcium, aluminium, and magnesium ions does inhibit the reabsorption of moxifloxacin. Drugs that prolong the QT interval (e.g. pimozide) should not be given during treatment with moxifloxacin. Concomitant administration of NSAIDs may lead to an increased risk of seizures. The prothrombin time may be increased in patients treated with warfarin.

Information for Patients/'non-specialized people'

This section provides information for patients treated with moxifloxacin or those people 'non-specialized' but interested in medicine/pharmacology:

Moxifloxacin (brand names Avelox®, Avalox®, or Vigamox® (eyedrops) for treating local infections of the eyes such as conjunctivitis) is a broad spectrum antibiotic belonging to the class of the so called 'gyrase-inhibitors'. Gyrase is an enzyme that is essential for progeny of bacteria, but not essential for human beings. Gyrase inhibitors kill a great variety of bacteria. Moxifloxacin is particular active and is therefore used to treat serious infections of the respiratory tract (sinusitis, acute flares of chronical bronichitis, coummunity acquired pneumonia). Other indications are severe infections of the skin or skin-structure, complicated intraabdominal infections, whether related to surgery or not. The drug may also be used to treat tuberculosis as part of a multidrug regime, particular if the disease is resistant to first-line agents. An additional indication is exposure to anthrax bacteria or clincally evident anthrax-disease.

The treatment duration is normally five to 7 days but may be up to 60 days in patients with anthrax-infection. The usual dosage is 400mg daily in a single dose. Commonly, the oral form (tablet) is used, but i.v. treatment is also possible, particular in a hospital setting.

Please consider that moxifloxacin may have a variety of side-effects, but it has been precribed because your type of infection is regarded serious and warrants treatment with a potent drug such as moxifloxacin. Most common side-effects are gastrointestinal reactions (nausea, vomiting, anorexia, bloating, abdominal pain, diarrhoea, and the serious condition pseudomembranous colitis marked by severe, sometimes bloody, diarrhea. Skin reactions are also common and may vary from mild (skin rash) to life-threatening (Stevens-Johnson syndrome). Central nervous system reactions are nervousness, sleeplessness, confusion, and rarely psychotic symptoms or seizures. These clinically relevant symptoms are reversible upon discontinuation of the drug. Rarely severe arrhythmias and tendon rupters are encountered.

If you experience more than mild side-effects, please do not terminate treatment on your own initiative, but discuss your concerns with a doctor. If you discontinue the drug too early your infection may reoccur and may even be fatal.

In case that you are either pregnant or breat-feeding discuss treatment with your doctor.

Please do not take moxifloaxacin together with antacids or milk, but wait a few hours, because the uptake of moxifloxacin in the body can be blocked. There are some other interactions that your doctor will have checked these before prescribing moxifloxacin.