BIOMOX 400MG TABLET

Indications

• Community-acquired pneumonia
• Acute exacerbation of chronic bronchitis
• Sinusitis
• Skin and soft tissue infections
• Intra-abdominal infections
• Pelvic inflammatory disease
• Uncomplicated urinary tract infections

Dosage

Adults: The usual adult dosage for moxifloxacin is 400 mg once daily, administered orally or intravenously.

Mechanism of action

Moxifloxacin exerts its bactericidal action by inhibiting the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV. These enzymes are critical for bacterial DNA replication, transcription, and repair. By interfering with these processes, moxifloxacin prevents the bacteria from successfully replicating, leading to cell death. Additionally, it has been shown to inhibit the hERG potassium K+ channel, which is associated with the prolongation of the QT interval, a cardiac risk factor.

Pharmacodynamics

As a quinolone/fluoroquinolone antibiotic, moxifloxacin is effective against a variety of bacteria. It is particularly active against aerobic Gram-positive bacteria, such as Staphylococcus aureus and Streptococcus pneumoniae, as well as aerobic Gram-negative bacteria, including Haemophilus influenzae. Moxifloxacin has a high affinity for bacterial DNA gyrase, being 100 times more selective for bacterial enzymes than for mammalian enzymes, which contributes to its efficacy and safety profile.

Pharmacokinetics

Moxifloxacin is well-absorbed following oral administration and has a bioavailability of approximately 90%. It is extensively distributed throughout the body, with a volume of distribution of around 2 to 3 L/kg. The drug undergoes hepatic metabolism, primarily via glucuronidation and oxidation, and is eliminated mainly through the urine. The half-life of moxifloxacin is approximately 12 hours, allowing for once-daily dosing in most cases.

Contra-indications

• Hypersensitivity to moxifloxacin or any other quinolone antibiotic
• History of tendon disorders related to fluoroquinolone use
• Patients with a history of myasthenia gravis

Adverse effects

• Nausea
• Diarrhea
• Headache
• Dizziness
• Rash
• QT interval prolongation
• Tendonitis and tendon rupture

Interactions

• Antacids containing magnesium, aluminum, or calcium can reduce moxifloxacin absorption
• Cationic drugs may interfere with moxifloxacin absorption
• Drugs that prolong the QT interval may increase the risk of arrhythmias when used with moxifloxacin

Precautions

• Caution in patients with a history of QT interval prolongation
• Use with caution in patients with renal impairment
• Monitor patients for signs of tendon injury
• Avoid in patients with a history of seizures

Pregnancy

Moxifloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Moxifloxacin is excreted in human milk. Caution should be exercised when administered to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• Tablets: 400 mg
• Intravenous infusion: 400 mg/250 mL

Mechanism of action

The bactericidal action of moxifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division. The fluoroquinolone antibiotic moxifloxacin has been associated with the acquired long QT syndrome and is used as a positive control in the evaluation of the QT-interval prolonging potential of new drugs. In common with other QT-prolonging agents, moxifloxacin is known to inhibit the hERG potassium K+ channel, but at present there is little mechanistic information available on this action. This study was conducted in order to characterise the inhibition of hERG current (I(hERG)) by moxifloxacin, and to determine the role in drug binding of the S6 aromatic amino-acid residues Tyr652 and Phe656. hERG currents were studied using whole-cell patch clamp (at room temperature and at 35-37 degrees C) in an HEK293 cell line stably expressing hERG channels. Moxifloxacin reversibly inhibited currents in a dose-dependent manner. We investigated the effects of different voltage commands to elicit hERG currents on moxifloxacin potency. Using a 'step-ramp' protocol, the IC50 was 65 uM at room temperature and 29 microM at 35 degrees C. When a ventricular action potential waveform was used to elicit currents, the IC50 was 114 microM. Block of hERG by moxifloxacin was found to be voltage-dependent, occurred rapidly and was independent of stimulation frequency. Mutagenesis of the S6 helix residue Phe656 to Ala failed to eliminate or reduce the moxifloxacin-mediated block whereas mutation of Tyr652 to Ala reduced moxifloxacin block by approximately 66%. Our data demonstrate that moxifloxacin blocks the hERG channel with a preference for the activated channel state. The Tyr652 but not Phe656 S6 residue is involved in moxifloxacin block of hERG, concordant with an interaction in the channel inner cavity. The bactericidal action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV required for bacterial DNA replication, transcription, repair, and recombination. It appears that the C8-methoxy moiety contributes to enhanced activity and lower selection of resistant mutants of Gram-positive bacteria compared to the C8-H moiety. The presence of the bulky bicycloamine substituent at the C-7 position prevents active efflux, associated with the NorA or pmrA genes seen in certain Gram-positive bacteria. Torsade de pointes (TdP) is increasingly recognized as a complication of drug therapy. The most common cause of drug-induced QT prolongation is inhibition of the rapidly activating component of the delayed potassium current (I(Kr)). Moxifloxacin, a widely used fluoroquinolone, is a weak I(Kr) inhibitor and has been associated with QT prolongation. Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels, especially the rapid component of the delayed rectifier potassium current I(Kr), expressed by HERG (the human ether-a-go-go-related gene). According to the available case reports and clinical studies, moxifloxacin carries the greatest risk of QT prolongation from all available quinolones in clinical practice and it should be used with caution in patients with predisposing factors for Torsades de pointes (TdP).

Pharmacodynamics

Moxifloxacin is a quinolone/fluoroquinolone antibiotic. Moxifloxacin can be used to treat infections caused by the following bacteria: Aerobic Gram-positive microorganisms: _Corynebacterium_ species, _Micrococcus luteus_, _Staphylococcus aureus_, _Staphylococcus epidermidis_, _Staphylococcus haemolyticus_, _Staphylococcus hominis_, _Staphylococcus warneri_, _Streptococcus pneumoniae_, and _Streptococcus viridans_ group. Aerobic Gram-negative microorganisms: _Acinetobacter lwoffii_, _Haemophilus influenzae_, and _Haemophilus parainfluenzae_. Other microorganisms: _Chlamydia trachomatis_. Moxifloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Moxifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.