ACTIGEM 320 TABLETS

Indications

• Acute bacterial exacerbation of chronic bronchitis
• Community-acquired pneumonia
• Uncomplicated skin and skin structure infections
• Acute sinusitis

Dosage

Children: Refer to the BNF for Children for dosage recommendations specific to paediatric patients.

Adults: The usual adult dose is 320 mg orally once daily for 5 to 7 days, depending on the type and severity of the infection.

Mechanism of action

The bactericidal action of gemifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination. Gemifloxacin inhibits DNA synthesis in susceptible organisms by blocking these type II DNA topoisomerases. It has a significantly higher affinity for bacterial DNA gyrase compared to mammalian enzymes, making it selectively toxic to bacteria.

Pharmacodynamics

Gemifloxacin is a quinolone/fluoroquinolone antibiotic that exerts a bactericidal effect. Its mechanism involves blocking bacterial DNA replication by binding to DNA gyrase, facilitating the untwisting of DNA required for replication. This action leads to cell death. Gemifloxacin is effective against a range of bacteria, including strains of Streptococcus pneumoniae that may be resistant to other fluoroquinolones.

Pharmacokinetics

Gemifloxacin is well absorbed orally and achieves high tissue concentrations. It is primarily excreted via the kidneys, and its half-life allows for once-daily dosing in most situations. The pharmacokinetics of gemifloxacin may be influenced by renal function, necessitating dose adjustments in patients with impaired renal clearance.

Contra-indications

• Hypersensitivity to gemifloxacin or other fluoroquinolones
• History of tendon disorders related to fluoroquinolone use
• Myasthenia gravis

Adverse effects

• Gastrointestinal disturbances (nausea, diarrhea)
• Headache
• Dizziness
• Rash
• Tendon rupture or tendonitis
• QT interval prolongation
• Photosensitivity reactions

Interactions

• Antacids, sucralfate, or supplements containing iron or zinc may reduce absorption
• Corticosteroids may increase the risk of tendon rupture
• NSAIDs may increase the risk of CNS stimulation
• Warfarin may enhance anticoagulant effect when co-administered

Precautions

• Use with caution in patients with a history of seizures
• Monitor for signs of tendon pain or inflammation during treatment
• Caution with patients having renal impairment; dosage adjustments may be necessary
• Assess for potential QT prolongation in patients with risk factors

Pregnancy

Gemifloxacin is classified as pregnancy category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Gemifloxacin is excreted in breast milk. Caution is advised when administering to nursing mothers, and alternative therapies may be considered.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets: 320 mg

Mechanism of action

The bactericidal action of gemifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination. Like other fluoroquinolone anti-infective agents, gemifloxacin inhibits DNA synthesis in susceptible organisms via inhibition of type II DNA topoisomerases (DNA gyrase, topoisomerase IV). However, unlike many other fluoroquinolones, gemifloxacin targets both DNA gyrase and topoisomerase IV in susceptible S. pneumoniae. Although cross-resistance can occur between gemifloxacin and other fluoroquinolones, gemifloxacin may be active against some strains of S. pneumoniae resistant to ciprofloxacin and other fluoroquinolones. The fluroquinolone gemifloxacin was examined for its capacity to modulate secretion of cytokines by human monocytes stimulated with lipopolysaccharide (LPS). Monocytes from six male and two female healthy volunteers were stimulated with LPS, exposed to gemifloxacin and the amounts of secreted IL-1 alpha, IL-1 beta, IL-6, IL-10 and TNF-alpha measured at 3, 6 and 24 h. The results revealed that LPS alone increased secretion of each cytokine significantly. Treatment of the LPS-stimulated monocytes with gemifloxacin resulted in a significant inhibition (p < 0.01) of secretion of each of the cytokines from monocytes of the eight volunteers. Nuclear extracts of the human monocyte cell line, THP-1, were used in the electrophoretic mobility shift assay to determine whether gemifloxacin affects nuclear factor-kappa B (NF-kappa B) activation. In addition, RNA from THP-1 cells was used in Northern blots to determine whether inhibition of secretion of IL-1 beta and TNF-alpha by gemifloxacin occurred at the transcription or translation level. Whereas LPS induced a rapid increase in NF-kappa B activation, gemifloxacin alone did not. Gemifloxacin did not affect the kinetics or decrease the extent of activation. Northern blots indicated that the inhibitory activity of gemifloxacin occurred post-transcription. Thus, gemifloxacin may modulate the immune response by altering secretion of cytokines by human monocytes. Although the concentrations of gemifloxacin used were higher than those observed in the serum of human volunteers treated with the dose under clinical development, it should be taken into consideration that concentrations at tissue and intracellular levels may be considerably higher than serum concentrations. 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

Gemifloxacin is a quinolone/fluoroquinolone antibiotic. Gemifloxacin 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. Gemifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.