Moxifloxacin

Moxifloxacin

Clinical data
Pregnancy category	C (US) B3 (Australia)
Routes of administration	Oral, IV
ATC code	J01MA14 (WHO)
Legal status
Legal status	US: WARNING Prescription Only
Pharmacokinetic data
Bioavailability	86 to 92%
Protein binding	30 to 50%
Metabolism	Glucuronide and sulfate conjugation Cytochrome P450 system not involved
Elimination half-life	12 hours
Excretion	Biliary and renal
Identifiers
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
CAS Number	354812-41-2
PubChem CID	152946
DrugBank	APRD00281
CompTox Dashboard (EPA)	DTXSID3048491
ECHA InfoCard	100.129.459
Chemical and physical data
Formula	C21H24FN3O4
Molar mass	401.431 g/mol g·mol−1

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. Currently, the drug is very popular.

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 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. 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, Klebsiella, Moraxella, Enterobacter, Mycobacteria and Anthrax.

Pharmacodynamic Data including Metabolization/Excretion

• Bioavailability : 86 to 92%, not influenced by meals
• Peak Plasma Level : 0.5 to 4 hours after oral dosing
• Time needed to reach steady-state : at least 3 days
• Half-life in normal individuals : approximately 12 hours, making once-a-day administration feasible
• 52 percent of the drug is metabolized via glucoronide and sulfate conjugates, which are pharmacological inactive. Enzymes of the CYP-class are not involved.
• The drug and the conjugates are excreted as well in urine and biliar/in feces.

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

• Respiratory infections including acute sinusitis, acute exacerbations of chronic bronchitis and community-acquired pneumonia
• Skin and skin structure infections

Investigational and Off-Label Uses

• Acute mycobacterial infections including tuberculosis as part of a multi-drug treatment regime
• The US Working Group on Civilian Biodefense has proposed that moxifloxacin should be used for the post-exposure prophylaxis and treatment of Anthrax.

Moxifloxacin is also used for the treatment of Complicated Intra-abdominal infections, as seen in the hospital.

Opthalmological Use

Moxifloxacin is also available as eyedrops to cure conjunctival infections caused by susceptible bacteria.

Contraindication

Known hypersensitivity to moxifloxacin or any other ingredient of the preparation

Use in pediatric Patients

There is no sufficient clinical data in patients under 18 yrs. of age.

Geriatric Patients

No dose reductions are necessary.

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

All typical side effects including GI-Tract disturbances (nausea, vomiting, anorexia, bloating, abdominal pain, diarrhea, and pseudomembraneous colitis caused by Clostridium difficile), skin reactions (also Steven-Johnson-syndrome), muscle wasting, and serious heart problems (QT-Time-Prolongation and Torsade de Pointes) are encountered. Development of resistance has been noticed as well as rare cases of hepatotoxicity and seizures. Ruptures of shoulder, hand, achilles and other tendons also occur.

Interactions

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

Dosage

400mg daily orally or via i.v.-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.