FLUOMIZIN

Indications

• Bacterial infections
• Fungal infections
• Protozoal infections
• Local antiseptic applications
• HIV-1 infection
• Leukemia treatment

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Dequalinium acts by disrupting bacterial cell permeability upon absorption into the bacterial cell surface. It denatures proteins involved in the respiratory chain and glycolysis, thus impairing bacterial metabolism. The drug inhibits mitochondrial ATP synthesis by blocking bacterial F1-ATPase, leading to energy depletion. Additionally, it intercalates with nucleic acids, potentially causing cell lysis through osmotic imbalance.

Pharmacodynamics

In vitro studies show that dequalinium exhibits rapid bactericidal and fungicidal activity against both gram-positive and gram-negative organisms, with sensitivity varying between species. Its minimal inhibitory concentration (MIC) against vaginal pathogens can range from 0.2 to ≥ 1024 µg/mL. Dequalinium also demonstrates anticancer effects by inducing apoptosis in leukemia cells through modulation of redox balance and downregulation of specific signaling pathways. Furthermore, it has noted antiviral properties, particularly against HIV-1.

Pharmacokinetics

The pharmacokinetics of dequalinium are characterized by rapid uptake by bacteria, leading to effective concentrations at the site of action. Its accumulation in mitochondria contributes to its mechanism as a mitochondrial poison. Specific absorption, distribution, metabolism, and excretion profiles in humans are not well-documented, necessitating cautious use in clinical settings.

Adverse effects

• Local irritation
• Allergic reactions
• Nausea
• Vomiting

Precautions

• Use with caution in patients with known hypersensitivity to dequalinium or quaternary ammonium compounds.
• Monitor for signs of local irritation or allergic reaction.

Pregnancy

There is limited data on the use of dequalinium in pregnancy. Use only if clearly needed and if the benefits outweigh the risks.

Breast-feeding

It is not known whether dequalinium is excreted in human milk. Caution is advised when administering to breastfeeding women.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Topical solution
• Vaginal tablets

Indications

• Bacterial vaginosis
• Trichomonal infections
• Other vaginal and vulval infections

Dosage

Adults: For adults aged 18 to 55 years, 10 mg once daily for 6 days, inserted intravaginally.

Mechanism of action

Dequalinium chloride disrupts bacterial cell membranes by diffusing through the cell wall, leading to increased cell permeability. It denatures proteins involved in bacterial metabolism and inhibits mitochondrial ATP synthesis by targeting F1-ATPase, thereby depleting bacterial energy sources. Additionally, it can intercalate into DNA, which may lead to cell lysis. These actions result in rapid bactericidal effects against various pathogens.

Pharmacodynamics

In vitro studies demonstrate that dequalinium is effective against both gram-positive and gram-negative bacteria, as well as fungi and protozoa. It exhibits rapid bactericidal and fungicidal activity, with effects observable within 30 to 60 minutes. Dequalinium's minimal inhibitory concentration (MIC) against relevant vaginal pathogens varies significantly, underscoring its potent antimicrobial properties. Moreover, it has shown potential anticancer effects in human leukemia cells through modulation of signaling pathways.

Pharmacokinetics

Dequalinium is administered intravaginally, where it acts locally with minimal systemic absorption. The pharmacokinetic profile in terms of absorption, distribution, metabolism, and excretion has not been extensively characterized, but its local action limits systemic exposure and potential side effects.

Contra-indications

• Vaginal ulceration
• Increased risk of infection

Adverse effects

• Skin reactions
• Constipation
• Diarrhoea
• Dizziness
• Gastrointestinal discomfort
• Headache
• Increased risk of infection
• Nausea
• Vertigo
• Vomiting
• Vulvovaginal irritation

Interactions

• Damages latex condoms and diaphragms
• Avoid use of non-latex condoms and intravaginal devices

Precautions

• Use during pregnancy only if essential due to limited information available

Pregnancy

Manufacturer advises to avoid unless essential; limited information available.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Dequalinium chloride 10 mg vaginal tablets
• Fluomizin 10 mg vaginal tablets

Mechanism of action

Dequalinium has multiple modes of action. Dequalinium absorbs into the bacterial cell surface and diffuses through the cell wall, disrupting bacterial cell permeability. It is taken up by the bacteria rapidly. Once in the bacteria, dequalinium denatures proteins involved in the respiratory chain and glycolysis of bacteria, interfering with bacterial cell metabolism and ribosomal protein synthesis. By inhibiting bacterial F1-ATPase, dequalinium inhibits mitochondrial ATP synthesis and blocks glucose metabolism. These molecular actions ultimately deplete bacterial energy sources. As dequalinium accumulates in the mitochondria, it is considered a mitochondrial poison. Dequalinium can also precipitate nucleic acids, as it can intercalate one of its quinoline chromophores between DNA base pairs. Depending on the drug concentration, dequalinium can lyse the bacterial cell by promoting osmotic imbalance.

Pharmacodynamics

_In vitro_, dequalinium possesses antimicrobial activity against gram-positive and gram-negative bacteria, yeasts, and protozoa. Dequalinium has a rapid bactericidal and fungicidal action. The antiparasitic and antiviral properties of dequalinium have also been noted. For example, dequalinium can bind to the membrane-proximal external region (MPER) of the spike envelope of the human immunodeficiency virus HIV-1. As with other quaternary ammonium compounds similar to dequalinium, gram-positive bacteria are more sensitive to dequalinium than gram-negative bacteria. The bactericidal and fungicidal effects of dequalinium can occur within 30 to 60 minutes. According to _in vitro_ studies, the minimal inhibitory concentration (MIC) for dequalinium against relevant vaginal pathogens ranges from 0.2 to ≥ 1024 µg/mL. There is evidence that dequalinium exhibits anticancer activity in human leukemia cells: dequalinium induces a cytotoxic effect by altering redox balance, downregulating Raf/MEK/ERK1/2 and PI3K/Akt signalling pathways, and promoting apoptosis of leukemic cells. Dequalinium was also shown to block small conductance Ca²⁺-activated K⁺ channels, called SK channels, which are often expressed in some cancer cells to play a role in cell proliferation and migration. One study showed that dequalinium reduced macrophage motility in mice, inhibiting macrophage infiltration of irradiated tumours and attenuating local metastasis. Interestingly, dequalinium was shown to modulate and induce self-oligomerization of alpha-synuclein, a synaptic protein known to cause aggregates in several neurodegenerative disorders. This finding highlights the neuroprotective actions of dequalinium; however, further investigations are warranted as dequalinium is a neurotoxic agent.

Mechanism of action

Dequalinium has multiple modes of action. Dequalinium absorbs into the bacterial cell surface and diffuses through the cell wall, disrupting bacterial cell permeability. It is taken up by the bacteria rapidly. Once in the bacteria, dequalinium denatures proteins involved in the respiratory chain and glycolysis of bacteria, interfering with bacterial cell metabolism and ribosomal protein synthesis. By inhibiting bacterial F1-ATPase, dequalinium inhibits mitochondrial ATP synthesis and blocks glucose metabolism. These molecular actions ultimately deplete bacterial energy sources. As dequalinium accumulates in the mitochondria, it is considered a mitochondrial poison. Dequalinium can also precipitate nucleic acids, as it can intercalate one of its quinoline chromophores between DNA base pairs. Depending on the drug concentration, dequalinium can lyse the bacterial cell by promoting osmotic imbalance.

Pharmacodynamics

_In vitro_, dequalinium possesses antimicrobial activity against gram-positive and gram-negative bacteria, yeasts, and protozoa. Dequalinium has a rapid bactericidal and fungicidal action. The antiparasitic and antiviral properties of dequalinium have also been noted. For example, dequalinium can bind to the membrane-proximal external region (MPER) of the spike envelope of the human immunodeficiency virus HIV-1. As with other quaternary ammonium compounds similar to dequalinium, gram-positive bacteria are more sensitive to dequalinium than gram-negative bacteria. The bactericidal and fungicidal effects of dequalinium can occur within 30 to 60 minutes. According to _in vitro_ studies, the minimal inhibitory concentration (MIC) for dequalinium against relevant vaginal pathogens ranges from 0.2 to ≥ 1024 µg/mL. There is evidence that dequalinium exhibits anticancer activity in human leukemia cells: dequalinium induces a cytotoxic effect by altering redox balance, downregulating Raf/MEK/ERK1/2 and PI3K/Akt signalling pathways, and promoting apoptosis of leukemic cells. Dequalinium was also shown to block small conductance Ca²⁺-activated K⁺ channels, called SK channels, which are often expressed in some cancer cells to play a role in cell proliferation and migration. One study showed that dequalinium reduced macrophage motility in mice, inhibiting macrophage infiltration of irradiated tumours and attenuating local metastasis. Interestingly, dequalinium was shown to modulate and induce self-oligomerization of alpha-synuclein, a synaptic protein known to cause aggregates in several neurodegenerative disorders. This finding highlights the neuroprotective actions of dequalinium; however, further investigations are warranted as dequalinium is a neurotoxic agent.